2. Academic Validation
  3. Ad-VT enhances the sensitivity of chemotherapy-resistant lung adenocarcinoma cells to gemcitabine and paclitaxel in vitro and in vivo

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

  • Invest New Drugs. 2022 Apr;40(2):274-289. doi: 10.1007/s10637-021-01204-4.
Gaojie Song 1 2 3,  Chao Shang 2,  Lili Sun 4,  Yiquan Li 3,  Yilong Zhu 3,  Zhiru Xiu 3,  Zirui Liu 2,  Yaru Li 3,  Xia Yang 3,  Chenchen Ge 3,  Jinbo Fang 5,  Ningyi Jin 6 7 8,  Xiao Li 9 10
Affiliations

Affiliations

  • 1 Medical College, Yanbian University, Yanji, China.
  • 2 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
  • 3 Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China.
  • 4 Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, China.
  • 5 Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China. fangjb@ccucm.edu.cn.
  • 6 Medical College, Yanbian University, Yanji, China. ningyik@126.com.
  • 7 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China. ningyik@126.com.
  • 8 Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China. ningyik@126.com.
  • 9 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China. lixiao06@mails.jlu.edu.cn.
  • 10 Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China. lixiao06@mails.jlu.edu.cn.
PMID: 34981275 DOI: 10.1007/s10637-021-01204-4
Abstract

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.

Keywords

Apoptosis; Autophagy; Lung cancer cells; Oncolytic virus; P-gp.

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