Inhibitory effect of Ubenimex combined with fluorouracil on multiple drug resistance and P‐glycoprotein expression level in non‐small lung cancer
Tumour drug resistance is one of the most urgent issues faced by anti‐tumour therapies. P‐glycoprotein (P‐gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. I...
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| description | Tumour drug resistance is one of the most urgent issues faced by anti‐tumour therapies. P‐glycoprotein (P‐gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. In this study, the tumour inhibitory role of 5FU and UBE was assessed in nude mice bearing A549 or A549/ADR. Real‐time polymerase chain reaction, Western blot and immunohistochemical were performed to analyse the mRNA and protein expression of P‐gp. TUNEL assay was used to evaluate the apoptosis of A549/ADR cells under 5FU and UBE treatment. MTT assay was performed to calculate the IC50 value of 5FU and UBE in A549 or A549/ADR. Combined administration of 5FU and UBE significantly inhibited the tumour growth of multidrug‐resistant cell lines A549/ADR in nude mice by down‐regulating the mRNA and protein expression of P‐gp. The apoptosis of A549/ADR was remarkably elevated in nude mice treated with 5FU and UBE. The IC50 value of 5FU and UBE was dramatically declined in A549/ADR cells compared with that of 5FU or UBE alone. Combined treatment of 5FU and UBE remarkably enhanced the apoptosis of A549/ADR cells by enhancing the intracellular accumulation of the drugs. The results of this study demonstrated that UBE combined with fluorouracil attenuated multiple drug resistance and inhibited the expression of P‐gp in lung cancer. |
| doi_str_mv | 10.1111/jcmm.15875 |
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P‐glycoprotein (P‐gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. In this study, the tumour inhibitory role of 5FU and UBE was assessed in nude mice bearing A549 or A549/ADR. Real‐time polymerase chain reaction, Western blot and immunohistochemical were performed to analyse the mRNA and protein expression of P‐gp. TUNEL assay was used to evaluate the apoptosis of A549/ADR cells under 5FU and UBE treatment. MTT assay was performed to calculate the IC50 value of 5FU and UBE in A549 or A549/ADR. Combined administration of 5FU and UBE significantly inhibited the tumour growth of multidrug‐resistant cell lines A549/ADR in nude mice by down‐regulating the mRNA and protein expression of P‐gp. The apoptosis of A549/ADR was remarkably elevated in nude mice treated with 5FU and UBE. The IC50 value of 5FU and UBE was dramatically declined in A549/ADR cells compared with that of 5FU or UBE alone. Combined treatment of 5FU and UBE remarkably enhanced the apoptosis of A549/ADR cells by enhancing the intracellular accumulation of the drugs. The results of this study demonstrated that UBE combined with fluorouracil attenuated multiple drug resistance and inhibited the expression of P‐gp in lung cancer.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.15875</identifier><identifier>PMID: 32945069</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>5-Fluorouracil ; 5FU ; A549 Cells ; Animals ; Antibodies ; Apoptosis ; Apoptosis - drug effects ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Survival - drug effects ; Chemotherapy ; Doxorubicin - pharmacology ; Doxorubicin - therapeutic use ; Drug resistance ; Drug Resistance, Multiple - drug effects ; Drug Resistance, Neoplasm - drug effects ; Fluorouracil - administration & dosage ; Fluorouracil - pharmacology ; Fluorouracil - therapeutic use ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Glycoproteins ; Humans ; Leucine - administration & dosage ; Leucine - analogs & derivatives ; Leucine - pharmacology ; Leucine - therapeutic use ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Metastasis ; Mice, Inbred C57BL ; Mice, Nude ; mRNA ; Multidrug resistance ; multiple drug resistance ; Original ; Penicillin ; Polymerase chain reaction ; Proteins ; P‐gp ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Tumors ; Ubenimex</subject><ispartof>Journal of cellular and molecular medicine, 2020-11, Vol.24 (21), p.12840-12847</ispartof><rights>2020 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4485-f4e9fb0967606f00f956f7295c82f152067cc9478e4c7da6b298d122963663ad3</citedby><cites>FETCH-LOGICAL-c4485-f4e9fb0967606f00f956f7295c82f152067cc9478e4c7da6b298d122963663ad3</cites><orcidid>0000-0003-4536-5647</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687002/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687002/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32945069$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wan, Jun</creatorcontrib><creatorcontrib>Ling, Xie‐an</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Ding, Guang‐gui</creatorcontrib><creatorcontrib>Wang, Xi</creatorcontrib><title>Inhibitory effect of Ubenimex combined with fluorouracil on multiple drug resistance and P‐glycoprotein expression level in non‐small lung cancer</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Tumour drug resistance is one of the most urgent issues faced by anti‐tumour therapies. P‐glycoprotein (P‐gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. In this study, the tumour inhibitory role of 5FU and UBE was assessed in nude mice bearing A549 or A549/ADR. Real‐time polymerase chain reaction, Western blot and immunohistochemical were performed to analyse the mRNA and protein expression of P‐gp. TUNEL assay was used to evaluate the apoptosis of A549/ADR cells under 5FU and UBE treatment. MTT assay was performed to calculate the IC50 value of 5FU and UBE in A549 or A549/ADR. Combined administration of 5FU and UBE significantly inhibited the tumour growth of multidrug‐resistant cell lines A549/ADR in nude mice by down‐regulating the mRNA and protein expression of P‐gp. The apoptosis of A549/ADR was remarkably elevated in nude mice treated with 5FU and UBE. The IC50 value of 5FU and UBE was dramatically declined in A549/ADR cells compared with that of 5FU or UBE alone. Combined treatment of 5FU and UBE remarkably enhanced the apoptosis of A549/ADR cells by enhancing the intracellular accumulation of the drugs. The results of this study demonstrated that UBE combined with fluorouracil attenuated multiple drug resistance and inhibited the expression of P‐gp in lung cancer.</description><subject>5-Fluorouracil</subject><subject>5FU</subject><subject>A549 Cells</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Survival - drug effects</subject><subject>Chemotherapy</subject><subject>Doxorubicin - pharmacology</subject><subject>Doxorubicin - therapeutic use</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple - 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drug effects</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell Survival - drug effects</topic><topic>Chemotherapy</topic><topic>Doxorubicin - pharmacology</topic><topic>Doxorubicin - therapeutic use</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple - drug effects</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Fluorouracil - administration & dosage</topic><topic>Fluorouracil - pharmacology</topic><topic>Fluorouracil - therapeutic use</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Glycoproteins</topic><topic>Humans</topic><topic>Leucine - administration & dosage</topic><topic>Leucine - analogs & derivatives</topic><topic>Leucine - pharmacology</topic><topic>Leucine - therapeutic use</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Metastasis</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Nude</topic><topic>mRNA</topic><topic>Multidrug resistance</topic><topic>multiple drug resistance</topic><topic>Original</topic><topic>Penicillin</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>P‐gp</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Tumors</topic><topic>Ubenimex</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wan, Jun</creatorcontrib><creatorcontrib>Ling, Xie‐an</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Ding, Guang‐gui</creatorcontrib><creatorcontrib>Wang, Xi</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><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>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>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>Engineering Research Database</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>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wan, Jun</au><au>Ling, Xie‐an</au><au>Wang, Jian</au><au>Ding, Guang‐gui</au><au>Wang, Xi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory effect of Ubenimex combined with fluorouracil on multiple drug resistance and P‐glycoprotein expression level in non‐small lung cancer</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2020-11</date><risdate>2020</risdate><volume>24</volume><issue>21</issue><spage>12840</spage><epage>12847</epage><pages>12840-12847</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Tumour drug resistance is one of the most urgent issues faced by anti‐tumour therapies. P‐glycoprotein (P‐gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. In this study, the tumour inhibitory role of 5FU and UBE was assessed in nude mice bearing A549 or A549/ADR. Real‐time polymerase chain reaction, Western blot and immunohistochemical were performed to analyse the mRNA and protein expression of P‐gp. TUNEL assay was used to evaluate the apoptosis of A549/ADR cells under 5FU and UBE treatment. MTT assay was performed to calculate the IC50 value of 5FU and UBE in A549 or A549/ADR. Combined administration of 5FU and UBE significantly inhibited the tumour growth of multidrug‐resistant cell lines A549/ADR in nude mice by down‐regulating the mRNA and protein expression of P‐gp. The apoptosis of A549/ADR was remarkably elevated in nude mice treated with 5FU and UBE. The IC50 value of 5FU and UBE was dramatically declined in A549/ADR cells compared with that of 5FU or UBE alone. Combined treatment of 5FU and UBE remarkably enhanced the apoptosis of A549/ADR cells by enhancing the intracellular accumulation of the drugs. The results of this study demonstrated that UBE combined with fluorouracil attenuated multiple drug resistance and inhibited the expression of P‐gp in lung cancer.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>32945069</pmid><doi>10.1111/jcmm.15875</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4536-5647</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 5-Fluorouracil 5FU A549 Cells Animals Antibodies Apoptosis Apoptosis - drug effects ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Cancer therapies Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology Cell Survival - drug effects Chemotherapy Doxorubicin - pharmacology Doxorubicin - therapeutic use Drug resistance Drug Resistance, Multiple - drug effects Drug Resistance, Neoplasm - drug effects Fluorouracil - administration & dosage Fluorouracil - pharmacology Fluorouracil - therapeutic use Gene expression Gene Expression Regulation, Neoplastic - drug effects Glycoproteins Humans Leucine - administration & dosage Leucine - analogs & derivatives Leucine - pharmacology Leucine - therapeutic use Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - pathology Metastasis Mice, Inbred C57BL Mice, Nude mRNA Multidrug resistance multiple drug resistance Original Penicillin Polymerase chain reaction Proteins P‐gp RNA, Messenger - genetics RNA, Messenger - metabolism Tumors Ubenimex |
| title | Inhibitory effect of Ubenimex combined with fluorouracil on multiple drug resistance and P‐glycoprotein expression level in non‐small lung cancer |
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