Objective. Conditionally replicating adenoviruses (CRAds) have been proven potent oncolytic viruses in previous studies. They selectively replicate in the
tumor cells because of incorporated
survivin promoter and ultimately lead to their killing with minimal side effects on normal tissue.
Chemotherapy with
cisplatin is commonly employed for treating
tumors, but its cytotoxic effects and development of resistance remained major concerns to be dealt with. The aim of this study was to explore the anticancer potential of
survivin regulated CRAd alone or in combination with
cisplatin in the A549
lung cancer cell line and
cisplatin-resistant
lung cancer cell line, A549-DDPR. Methods. CRAd was genetically engineered in our laboratory by removing its E1B region and adding
survivin promoter to control its replication. A549, H292, and H661
lung cancer cell lines were procured from the CAS-China. The anti-
tumor effectiveness of combined treatment (
cisplatin plus CRAd) was evaluated in vitro through MTS assays and in vivo through mouse model experimentation. RT- PCR was used to assess MDR gene and
mRNA expression of coxsackie adenoviral receptor (CAR). Results. Results of in vitro studies established that A549
lung cancer cells were highly sensitive to
cisplatin showing dose-dependent inhibition. The resistant cells of A549-DDPR exhibited very less sensitivity to
cisplatin but were infected with CRAd more efficiently as compared to A549. A549-DDPR cells exhibited higher expression of MDR gene and CAR in the RT-PCR analysis. The nearly similar rise in the CAR expression was seen when
lung cancer cell lines received
cisplatin in combined treatment (
cisplatin plus CRAd). Combined anti-
cancer therapy (
cisplatin plus oncolytic virus) proved more efficient than monotherapy in the killing of
cancer cells. Results of in vivo experiments recapitulated nearly similar
tumor inhibition activities. Conclusion. This study highlighted the significant role of
survivin in gene therapy as it has the potential to render CRAd more
tumor specific. It also establishes that higher CAR expression plays a vital role in the success of adenovirus-based
therapies. Furthermore, a careful combination of
chemotherapy drugs and oncolytic viruses can culminate in significant therapeutic achievements against
cancer.