Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and interferon-α2b on the murine Renca renal cell carcinoma cell line in vitro and in vivo
Novel therapeutic strategies to improve clinical efficacy in patients with renal cell carcinoma (RCC) are required. The possibility of combination therapy with Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)-α2b remains to be elucidated in RCC. The present study investigated t...
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| Veröffentlicht in: | Molecular medicine reports 2015-11, Vol.12 (5), p.6727-6737 |
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| creator | CHEN, SHIYOU LIANG, LUNAN WANG, YING DIAO, JIANHUN ZHAO, CHUNXIONG CHEN, GANG HE, YUNFENG LUO, CHUNLI WU, XIAOHOU ZHANG, YAO |
| description | Novel therapeutic strategies to improve clinical efficacy in patients with renal cell carcinoma (RCC) are required. The possibility of combination therapy with Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)-α2b remains to be elucidated in RCC. The present study investigated the putative synergistic immunotherapeutic roles of LBP and IFN-α2b against RCC in vitro and in vivo. The mouse RCC cell line, Renca, was used for in vitro experiments. Treatment of the cells with a combination of LBP and IFN-α2b markedly inhibited cell proliferation, retarded cell cycle growth and promoted apoptosis in the Renca cells. Western blot analysis revealed that LBP and IFN-α2b synergistically downregulated the expression levels of cyclin D1, c-Myc and Bcl-2, and upregulated the expression of the antiapoptotic protein, Bax. Myeloid-derived suppressor cells (MDSCs) were markedly upregulated during tumour progression and promoted tumour growth by inhibiting the T-cell-mediated immune response. In vivo, a marked reduction in the MDSC ratio and tumour volume was observed in a group receiving combined treatment with LBP and IFN-α2b in a xenograft tumour model. In conclusion, the present study suggested that the combination of LBP and IFN-α2b is likely to be more effective in treating murine RCC compared with the less pronounced immunotherapeutic effects of administering LBP or IFN-α2b alone. |
| doi_str_mv | 10.3892/mmr.2015.4230 |
| format | Article |
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The possibility of combination therapy with Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)-α2b remains to be elucidated in RCC. The present study investigated the putative synergistic immunotherapeutic roles of LBP and IFN-α2b against RCC in vitro and in vivo. The mouse RCC cell line, Renca, was used for in vitro experiments. Treatment of the cells with a combination of LBP and IFN-α2b markedly inhibited cell proliferation, retarded cell cycle growth and promoted apoptosis in the Renca cells. Western blot analysis revealed that LBP and IFN-α2b synergistically downregulated the expression levels of cyclin D1, c-Myc and Bcl-2, and upregulated the expression of the antiapoptotic protein, Bax. Myeloid-derived suppressor cells (MDSCs) were markedly upregulated during tumour progression and promoted tumour growth by inhibiting the T-cell-mediated immune response. In vivo, a marked reduction in the MDSC ratio and tumour volume was observed in a group receiving combined treatment with LBP and IFN-α2b in a xenograft tumour model. In conclusion, the present study suggested that the combination of LBP and IFN-α2b is likely to be more effective in treating murine RCC compared with the less pronounced immunotherapeutic effects of administering LBP or IFN-α2b alone.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2015.4230</identifier><identifier>PMID: 26300071</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis ; Apoptosis - drug effects ; BAX protein ; Bcl-2 protein ; c-Myc protein ; Cancer therapies ; Carcinoma, Renal cell ; Carcinoma, Renal Cell - drug therapy ; Care and treatment ; Cell cycle ; Cell Cycle Checkpoints ; Cell growth ; Cell Line, Tumor ; Cell proliferation ; Chemotherapy ; Cyclin D1 ; Drug Screening Assays, Antitumor ; Drug Synergism ; Flow cytometry ; Goji berries ; Granulocytes ; Health aspects ; Humans ; Immune response (cell-mediated) ; Immunotherapy ; Interferon ; Interferon alfa-2b ; Interferon-alpha - pharmacology ; Kidney cancer ; Kidney Neoplasms - drug therapy ; Lycium - chemistry ; Lycium barbarum polysaccharide ; Lymphocytes T ; Male ; Metastasis ; Mice, Inbred BALB C ; murine renal cell carcinoma ; Myc protein ; Neoplasm Transplantation ; Plant Extracts - pharmacology ; Polysaccharides ; Polysaccharides - pharmacology ; recombinant interferon-α2b ; Recombinant Proteins - pharmacology ; Renal cell carcinoma ; renca cells ; Studies ; Suppressor cells ; Tumor Burden ; Tumors ; Xenografts</subject><ispartof>Molecular medicine reports, 2015-11, Vol.12 (5), p.6727-6737</ispartof><rights>Copyright: © Chen et al.</rights><rights>COPYRIGHT 2015 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2015</rights><rights>Copyright: © Chen et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4950-7867ca82efaf49053318baa619f91329111b291f864286484af3421a9fb5db83</citedby><cites>FETCH-LOGICAL-c4950-7867ca82efaf49053318baa619f91329111b291f864286484af3421a9fb5db83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,5571,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26300071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHEN, SHIYOU</creatorcontrib><creatorcontrib>LIANG, LUNAN</creatorcontrib><creatorcontrib>WANG, YING</creatorcontrib><creatorcontrib>DIAO, JIANHUN</creatorcontrib><creatorcontrib>ZHAO, CHUNXIONG</creatorcontrib><creatorcontrib>CHEN, GANG</creatorcontrib><creatorcontrib>HE, YUNFENG</creatorcontrib><creatorcontrib>LUO, CHUNLI</creatorcontrib><creatorcontrib>WU, XIAOHOU</creatorcontrib><creatorcontrib>ZHANG, YAO</creatorcontrib><title>Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and interferon-α2b on the murine Renca renal cell carcinoma cell line in vitro and in vivo</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>Novel therapeutic strategies to improve clinical efficacy in patients with renal cell carcinoma (RCC) are required. The possibility of combination therapy with Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)-α2b remains to be elucidated in RCC. The present study investigated the putative synergistic immunotherapeutic roles of LBP and IFN-α2b against RCC in vitro and in vivo. The mouse RCC cell line, Renca, was used for in vitro experiments. Treatment of the cells with a combination of LBP and IFN-α2b markedly inhibited cell proliferation, retarded cell cycle growth and promoted apoptosis in the Renca cells. Western blot analysis revealed that LBP and IFN-α2b synergistically downregulated the expression levels of cyclin D1, c-Myc and Bcl-2, and upregulated the expression of the antiapoptotic protein, Bax. Myeloid-derived suppressor cells (MDSCs) were markedly upregulated during tumour progression and promoted tumour growth by inhibiting the T-cell-mediated immune response. In vivo, a marked reduction in the MDSC ratio and tumour volume was observed in a group receiving combined treatment with LBP and IFN-α2b in a xenograft tumour model. In conclusion, the present study suggested that the combination of LBP and IFN-α2b is likely to be more effective in treating murine RCC compared with the less pronounced immunotherapeutic effects of administering LBP or IFN-α2b alone.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>c-Myc protein</subject><subject>Cancer therapies</subject><subject>Carcinoma, Renal cell</subject><subject>Carcinoma, Renal Cell - drug therapy</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cell Cycle Checkpoints</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Chemotherapy</subject><subject>Cyclin D1</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Drug Synergism</subject><subject>Flow cytometry</subject><subject>Goji berries</subject><subject>Granulocytes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immune response (cell-mediated)</subject><subject>Immunotherapy</subject><subject>Interferon</subject><subject>Interferon alfa-2b</subject><subject>Interferon-alpha - pharmacology</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - drug therapy</subject><subject>Lycium - chemistry</subject><subject>Lycium barbarum polysaccharide</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Metastasis</subject><subject>Mice, Inbred BALB C</subject><subject>murine renal cell carcinoma</subject><subject>Myc protein</subject><subject>Neoplasm Transplantation</subject><subject>Plant Extracts - pharmacology</subject><subject>Polysaccharides</subject><subject>Polysaccharides - pharmacology</subject><subject>recombinant interferon-α2b</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Renal cell carcinoma</subject><subject>renca cells</subject><subject>Studies</subject><subject>Suppressor cells</subject><subject>Tumor Burden</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptksuKFDEUhgtRnHF06VYCLnRTbS51y0YYBm_QIOjsQyp10p2hkrRJVUM_j0_gi_hMnrLbxhFJcnL78oeT_EXxnNGV6CR_431accrqVcUFfVBcslayUlBaPTyNuZTtRfEk5ztKm5rX8nFxwRskaMsui-9fDwHSxuXJGeK8n0OctpD0DuZlBawFM2USLVkfjJs96XXCioNdHA9ZG7PVyQ1AdBiICxMkCymG8ucP3pMYCIoRPycXgHyBYDRJEPRIDIwYdDIuRK-P03GBXCB7N6V40sPJPj4tHlk9Znh26q-K2_fvbm8-luvPHz7dXK9LU8malm3XtEZ3HKy2laS1EKzrtW6YtJIJLhljPUbbNRXH1lXaioozLW1fD30nroq3R9nd3HsYDIQp6VHtkvM6HVTUTt3fCW6rNnGvqoY3TEgUeH0SSPHbDHlS3uUlNR0gzlmxlrdSVrTmiL78B72Lc8KXQUoKXrWi-S14ojZ6BOWCjXivWUTVdSUk65pOCKRW_6GwDOCdiQGsw_V7B8rjAZNizgnsOUdG1WIqhaZSi6nUYirkX_z9MGf6j4sQeHUE8g6_zQ0xnxlUKhkvaV02mL34BSAE1xw</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>CHEN, SHIYOU</creator><creator>LIANG, LUNAN</creator><creator>WANG, YING</creator><creator>DIAO, JIANHUN</creator><creator>ZHAO, CHUNXIONG</creator><creator>CHEN, GANG</creator><creator>HE, YUNFENG</creator><creator>LUO, CHUNLI</creator><creator>WU, XIAOHOU</creator><creator>ZHANG, YAO</creator><general>D.A. 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pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>BAX protein</topic><topic>Bcl-2 protein</topic><topic>c-Myc protein</topic><topic>Cancer therapies</topic><topic>Carcinoma, Renal cell</topic><topic>Carcinoma, Renal Cell - drug therapy</topic><topic>Care and treatment</topic><topic>Cell cycle</topic><topic>Cell Cycle Checkpoints</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Chemotherapy</topic><topic>Cyclin D1</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Drug Synergism</topic><topic>Flow cytometry</topic><topic>Goji berries</topic><topic>Granulocytes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immune response (cell-mediated)</topic><topic>Immunotherapy</topic><topic>Interferon</topic><topic>Interferon alfa-2b</topic><topic>Interferon-alpha - pharmacology</topic><topic>Kidney cancer</topic><topic>Kidney Neoplasms - drug therapy</topic><topic>Lycium - chemistry</topic><topic>Lycium barbarum polysaccharide</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Metastasis</topic><topic>Mice, Inbred BALB C</topic><topic>murine renal cell carcinoma</topic><topic>Myc protein</topic><topic>Neoplasm Transplantation</topic><topic>Plant Extracts - pharmacology</topic><topic>Polysaccharides</topic><topic>Polysaccharides - pharmacology</topic><topic>recombinant interferon-α2b</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Renal cell carcinoma</topic><topic>renca cells</topic><topic>Studies</topic><topic>Suppressor cells</topic><topic>Tumor Burden</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHEN, SHIYOU</creatorcontrib><creatorcontrib>LIANG, LUNAN</creatorcontrib><creatorcontrib>WANG, YING</creatorcontrib><creatorcontrib>DIAO, JIANHUN</creatorcontrib><creatorcontrib>ZHAO, CHUNXIONG</creatorcontrib><creatorcontrib>CHEN, GANG</creatorcontrib><creatorcontrib>HE, YUNFENG</creatorcontrib><creatorcontrib>LUO, CHUNLI</creatorcontrib><creatorcontrib>WU, XIAOHOU</creatorcontrib><creatorcontrib>ZHANG, YAO</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHEN, SHIYOU</au><au>LIANG, LUNAN</au><au>WANG, YING</au><au>DIAO, JIANHUN</au><au>ZHAO, CHUNXIONG</au><au>CHEN, GANG</au><au>HE, YUNFENG</au><au>LUO, CHUNLI</au><au>WU, XIAOHOU</au><au>ZHANG, YAO</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and interferon-α2b on the murine Renca renal cell carcinoma cell line in vitro and in vivo</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2015-11</date><risdate>2015</risdate><volume>12</volume><issue>5</issue><spage>6727</spage><epage>6737</epage><pages>6727-6737</pages><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>Novel therapeutic strategies to improve clinical efficacy in patients with renal cell carcinoma (RCC) are required. The possibility of combination therapy with Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)-α2b remains to be elucidated in RCC. The present study investigated the putative synergistic immunotherapeutic roles of LBP and IFN-α2b against RCC in vitro and in vivo. The mouse RCC cell line, Renca, was used for in vitro experiments. Treatment of the cells with a combination of LBP and IFN-α2b markedly inhibited cell proliferation, retarded cell cycle growth and promoted apoptosis in the Renca cells. Western blot analysis revealed that LBP and IFN-α2b synergistically downregulated the expression levels of cyclin D1, c-Myc and Bcl-2, and upregulated the expression of the antiapoptotic protein, Bax. Myeloid-derived suppressor cells (MDSCs) were markedly upregulated during tumour progression and promoted tumour growth by inhibiting the T-cell-mediated immune response. In vivo, a marked reduction in the MDSC ratio and tumour volume was observed in a group receiving combined treatment with LBP and IFN-α2b in a xenograft tumour model. In conclusion, the present study suggested that the combination of LBP and IFN-α2b is likely to be more effective in treating murine RCC compared with the less pronounced immunotherapeutic effects of administering LBP or IFN-α2b alone.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26300071</pmid><doi>10.3892/mmr.2015.4230</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic Agents, Phytogenic - pharmacology Apoptosis Apoptosis - drug effects BAX protein Bcl-2 protein c-Myc protein Cancer therapies Carcinoma, Renal cell Carcinoma, Renal Cell - drug therapy Care and treatment Cell cycle Cell Cycle Checkpoints Cell growth Cell Line, Tumor Cell proliferation Chemotherapy Cyclin D1 Drug Screening Assays, Antitumor Drug Synergism Flow cytometry Goji berries Granulocytes Health aspects Humans Immune response (cell-mediated) Immunotherapy Interferon Interferon alfa-2b Interferon-alpha - pharmacology Kidney cancer Kidney Neoplasms - drug therapy Lycium - chemistry Lycium barbarum polysaccharide Lymphocytes T Male Metastasis Mice, Inbred BALB C murine renal cell carcinoma Myc protein Neoplasm Transplantation Plant Extracts - pharmacology Polysaccharides Polysaccharides - pharmacology recombinant interferon-α2b Recombinant Proteins - pharmacology Renal cell carcinoma renca cells Studies Suppressor cells Tumor Burden Tumors Xenografts |
| title | Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and interferon-α2b on the murine Renca renal cell carcinoma cell line in vitro and in vivo |
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