Ad-VT enhances the sensitivity of chemotherapy-resistant lung adenocarcinoma cells to gemcitabine and paclitaxel in vitro and in vivo

文献类型： 外文期刊

第一作者： Song, Gaojie

作者： Song, Gaojie;Jin, Ningyi;Song, Gaojie;Shang, Chao;Liu, Zirui;Jin, Ningyi;Li, Xiao;Song, Gaojie;Li, Yiquan;Zhu, Yilong;Xiu, Zhiru;Li, Yaru;Yang, Xia;Ge, Chenchen;Fang, Jinbo;Jin, Ningyi;Li, Xiao;Sun, Lili

作者机构：

关键词： Lung cancer cells; Oncolytic virus; Apoptosis; Autophagy; P-gp

期刊名称：INVESTIGATIONAL NEW DRUGS （ 影响因子：3.651； 五年影响因子：3.862 ）

ISSN： 0167-6997

年卷期： 2022 年 40 卷 2 期

页码：

收录情况： SCI

摘要： Background One of the main challenges in the clinical treatment of lung cancer is resistance to chemotherapeutic drugs. P-glycoprotein (P-gp)-mediated drug resistance is the main obstacle to successfully implementing microtubule-targeted tumor chemotherapy. Purpose In this study, we explored the effect of Ad-hTERTp-E1a-Apoptin (Ad-VT) on drug-resistant cell lines and the molecular mechanism by which Ad-VT combined with chemotherapy affects drug-resistant cells and parental cells. Methods In vitro, cell proliferation, colony formation, resistance index (RI), apoptosis and autophagy assays were performed. Protein expression was analyzed by Western blotting. Finally, a xenograft tumor model in nude mice was used to detect tumor growth and evaluate histological characteristics. Results Our results showed that Ad-VT had an obvious killing effect on A549, A549/GEM and A549/Paclitaxel cancer cells, and the sensitivity of drug-resistant cell lines to Ad-VT was significantly higher than that of parental A549 cells. Compared with A549 cells, A549/GEM and A549/Paclitaxel cells had higher autophagy levels and higher viral replication ability. Ad-VT decreased the levels of p-PI3k, p-Akt and p-mTOR and the expression of P-gp. In vivo, Ad-VT combined with chemotherapy can effectively inhibit the growth of chemotherapy-resistant tumors and prolong the survival of mice. Conclusions Thus, the combination of Ad-VT and chemotherapeutic drugs will be a promising strategy to overcome chemoresistance.

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