Abstract
Objective: The aim of the study was to improve the therapeutic effect for lung cancer using a synergetic strategy of adenovirus-based gene therapy combined with chemotherapy. Methods: A conditional replication adenovirus(CRAd) was employed to treat the A549 lung cancer cells and cisplatin-resisted A549(A549-DDP) cells. In vitro MTS / PMS assay were used to evaluate the cell viability. PCR were used to detect expression of Coxsackie receptor (CAR) and Multidrug resistance(MDR) gene. The in vivo anti-tumor effect of CRAd and cisplatin was evaluated using a subcutaneous mouse model. Results: The CRAd sensitizes A549 cancer cells to cisplatin. The mechanism of enhanced cell growth inhibition is associated with the increased CAR and MDR expression. Conclusion: Our approach is better than the conventional gene therapy and chemotherapy strategy.
Highlights
Lung cancer is a common malignancy [1], the majority of patients lost the chance of surgery when found, chemotherapy play a very important role in the clinical treatment of lung cancer and prolong survival in patients [2,3], but resistance of chemotherapy drug has hindered its development [4]
A549 (4 x 106), A549-DDP (4 ×106) cells were inoculated subcutaneous into the right flank of mice,tumor bearing mice(n = 6 per group) were divided into three groups.Mice in each group were treated as follow: (a) cisplatin treatment group (b) conditionally replicative adenovirus (CRAd) treatment group (c) cisplatin combined CRAd treatment group; Ad-luc virus transfected to each treatment group, a certain period of time to observe the effect by vivo imaging
3) Treated A549 and A549- DDP cells by combined with cisplatin and CRAd virus,we found that the inhibition of cell treated by the method mentioned at MTS/PMS assay group (d) is more obvious than group (c) on A549-DDP cell line
Summary
Lung cancer is a common malignancy [1], the majority of patients lost the chance of surgery when found, chemotherapy play a very important role in the clinical treatment of lung cancer and prolong survival in patients [2,3], but resistance of chemotherapy drug has hindered its development [4]. Overexpression of the MDR gene is one of the mechanisms leads to tumor cell multidrug resistance [5], while adenovirus cancer gene therapy has rapidly developed in natural medicine, conditionally replicative adenovirus (CRAd) is able to selectively copy in tumor cells and spread to more tumor cells, CRAd has a stronger tumor scavenging, and to reduce the liver toxic effects of less dosage. This experiment combined CRAd with the chemotherapy drug cisplatin, explore the effect and mechanisms of A549 and A549-DDP
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