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Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma

College of Life Science and Bioengineering, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang, Beijing 100124, China
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1125; https://doi.org/10.3390/ijms20051125
Received: 18 January 2019 / Revised: 9 February 2019 / Accepted: 27 February 2019 / Published: 5 March 2019
(This article belongs to the Special Issue Cisplatin in Cancer Therapy: Molecular Mechanisms of Action)
Cisplatin is ranked as one of the most powerful and commonly prescribed anti-tumor chemotherapeutic agents which improve survival in many solid tumors including non-small cell lung cancer. However, the treatment of advanced lung cancer is restricted due to chemotherapy resistance. Here, we developed and investigated survivin promoter regulating conditionally replicating adenovirus (CRAd) for its anti-tumor potential alone or in combination with cisplatin in two lung cancer cells, H23, H2126, and their resistant cells, H23/CPR, H2126/CPR. To measure the expression of genes which regulate resistance, adenoviral transduction, metastasis, and apoptosis in cancer cells, RT-PCR and Western blotting were performed. The anti-tumor efficacy of the treatments was evaluated through flow cytometry, MTT and transwell assays. This study demonstrated that co-treatment with cisplatin and CRAd exerts synergistic anti-tumor effects on chemotherapy sensitive lung cancer cells and monotherapy of CRAd could be a practical approach to deal with chemotherapy resistance. Combined treatment induced stronger apoptosis by suppressing the anti-apoptotic molecule Bcl-2, and reversed epithelial to mesenchymal transition. In conclusion, cisplatin synergistically increased the tumor-killing of CRAd by (1) increasing CRAd transduction via enhanced CAR expression and (2) increasing p53 dependent or independent apoptosis of lung cancer cell lines. Also, CRAd alone proved to be a very efficient anti-tumor agent in cancer cells resistant to cisplatin owing to upregulated CAR levels. In an exciting outcome, we have revealed novel therapeutic opportunities to exploit intrinsic and acquired resistance to enhance the therapeutic index of anti-tumor treatment in lung cancer. View Full-Text
Keywords: cisplatin; chemotherapy resistance; apoptosis; lung cancer cisplatin; chemotherapy resistance; apoptosis; lung cancer
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MDPI and ACS Style

Ali, S.; Tahir, M.; Khan, A.A.; Chen, X.C.; Ling, M.; Huang, Y. Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma. Int. J. Mol. Sci. 2019, 20, 1125. https://doi.org/10.3390/ijms20051125

AMA Style

Ali S, Tahir M, Khan AA, Chen XC, Ling M, Huang Y. Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma. International Journal of Molecular Sciences. 2019; 20(5):1125. https://doi.org/10.3390/ijms20051125

Chicago/Turabian Style

Ali, Sakhawat, Muhammad Tahir, Aamir A. Khan, Xue C. Chen, Ma Ling, and Yinghui Huang. 2019. "Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma" International Journal of Molecular Sciences 20, no. 5: 1125. https://doi.org/10.3390/ijms20051125

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