Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression
Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic a...
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| Veröffentlicht in: | Life sciences (1973) 2021-06, Vol.275, p.119369-119369, Article 119369 |
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| creator | Joshi, Navneet Hajizadeh, Farnaz Ansari Dezfouli, Ehsan Zekiy, Angelina Olegovna Nabi Afjadi, Mohsen Mousavi, Seyedeh Mahboubeh Hojjat-Farsangi, Mohammad Karpisheh, Vahid Mahmoodpoor, Ata Hassannia, Hadi Dolati, Sanam Mohammadi, Hamed Yousefi, Mehdi Jadidi-Niaragh, Farhad |
| description | Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death.
We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo.
The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses.
These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells. |
| doi_str_mv | 10.1016/j.lfs.2021.119369 |
| format | Article |
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We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo.
The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses.
These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2021.119369</identifier><identifier>PMID: 33745894</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Antibiotics, Antineoplastic - therapeutic use ; Apoptosis ; Cancer ; Cancer therapies ; Cell death ; Cell Line, Tumor ; Chemotherapy ; Chitosan ; Doxorubicin ; Doxorubicin - therapeutic use ; Drug resistance ; Drug Resistance, Neoplasm - genetics ; Female ; Folic acid ; Gene Silencing ; Humans ; Immune response ; Immunosuppressive agents ; Lactic acid ; Mice ; Mice, Inbred BALB C ; Nanoparticle ; Nanoparticles ; Neoplasm Transplantation ; Neoplasms - drug therapy ; Neoplasms - pathology ; Neoplasms - therapy ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - therapeutic use ; Sensitivity enhancement ; Side effects ; siRNA ; STAT3 ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; Transcriptome</subject><ispartof>Life sciences (1973), 2021-06, Vol.275, p.119369-119369, Article 119369</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Jun 15, 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-e26ada68e8262cbf9c7bba73f72ec30812c98dba7666f9ca9c86e09dcb407bdf3</citedby><cites>FETCH-LOGICAL-c419t-e26ada68e8262cbf9c7bba73f72ec30812c98dba7666f9ca9c86e09dcb407bdf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2021.119369$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33745894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:146549822$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Joshi, Navneet</creatorcontrib><creatorcontrib>Hajizadeh, Farnaz</creatorcontrib><creatorcontrib>Ansari Dezfouli, Ehsan</creatorcontrib><creatorcontrib>Zekiy, Angelina Olegovna</creatorcontrib><creatorcontrib>Nabi Afjadi, Mohsen</creatorcontrib><creatorcontrib>Mousavi, Seyedeh Mahboubeh</creatorcontrib><creatorcontrib>Hojjat-Farsangi, Mohammad</creatorcontrib><creatorcontrib>Karpisheh, Vahid</creatorcontrib><creatorcontrib>Mahmoodpoor, Ata</creatorcontrib><creatorcontrib>Hassannia, Hadi</creatorcontrib><creatorcontrib>Dolati, Sanam</creatorcontrib><creatorcontrib>Mohammadi, Hamed</creatorcontrib><creatorcontrib>Yousefi, Mehdi</creatorcontrib><creatorcontrib>Jadidi-Niaragh, Farhad</creatorcontrib><title>Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death.
We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo.
The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses.
These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Chitosan</subject><subject>Doxorubicin</subject><subject>Doxorubicin - therapeutic use</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Folic acid</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunosuppressive agents</subject><subject>Lactic acid</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nanoparticle</subject><subject>Nanoparticles</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - therapy</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - therapeutic use</subject><subject>Sensitivity enhancement</subject><subject>Side effects</subject><subject>siRNA</subject><subject>STAT3</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Transcriptome</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1P3DAQhq2qqCy0P4BLZamXXrL4I3FicUKoBSQkDixnyx8T8JK1t3ZC4d_XqywcOPRka-Z5X83Mi9AJJUtKqDhdL4c-LxlhdEmp5EJ-QgvatbIigtPPaEEIqyvOSHOIjnJeE0KapuVf0CHnbd10sl4gc-cHCNaHB3y3Ol9xDOFRBwsZZwjZj_7Zj6849tjuqglbGIaMx4hdfIlpMr5IsQ4O-_DojR9Lb9rEhLcpPiTI2cfwFR30esjwbf8eo_vfv1YXV9XN7eX1xflNZWsqxwqY0E6LDjommDW9tK0xuuV9y8By0lFmZedKRQhRmlraTgCRzpqatMb1_BhVs2_-C9vJqG3yG51eVdRe7UtP5QeqFrymXeF_znyZ9c8EeVQbn3f76QBxyoo1hAtBaSMK-uMDuo5TCmWbQjFaji9JXSg6UzbFnBP07yNQonaBqbUqgaldYGoOrGi-750nswH3rnhLqABnMwDldM8eksrWl8TA-QR2VC76_9j_Ax-2p8Q</recordid><startdate>20210615</startdate><enddate>20210615</enddate><creator>Joshi, Navneet</creator><creator>Hajizadeh, Farnaz</creator><creator>Ansari Dezfouli, Ehsan</creator><creator>Zekiy, Angelina Olegovna</creator><creator>Nabi Afjadi, Mohsen</creator><creator>Mousavi, Seyedeh Mahboubeh</creator><creator>Hojjat-Farsangi, Mohammad</creator><creator>Karpisheh, Vahid</creator><creator>Mahmoodpoor, Ata</creator><creator>Hassannia, Hadi</creator><creator>Dolati, Sanam</creator><creator>Mohammadi, Hamed</creator><creator>Yousefi, Mehdi</creator><creator>Jadidi-Niaragh, Farhad</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20210615</creationdate><title>Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression</title><author>Joshi, Navneet ; 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The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death.
We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo.
The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses.
These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>33745894</pmid><doi>10.1016/j.lfs.2021.119369</doi><tpages>1</tpages></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Antibiotics, Antineoplastic - therapeutic use Apoptosis Cancer Cancer therapies Cell death Cell Line, Tumor Chemotherapy Chitosan Doxorubicin Doxorubicin - therapeutic use Drug resistance Drug Resistance, Neoplasm - genetics Female Folic acid Gene Silencing Humans Immune response Immunosuppressive agents Lactic acid Mice Mice, Inbred BALB C Nanoparticle Nanoparticles Neoplasm Transplantation Neoplasms - drug therapy Neoplasms - pathology Neoplasms - therapy RNA, Small Interfering - administration & dosage RNA, Small Interfering - therapeutic use Sensitivity enhancement Side effects siRNA STAT3 Stat3 protein STAT3 Transcription Factor - metabolism Transcriptome |
| title | Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression |
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