Downregulation of survivin by adenovirus-mediated shRNA promotes apoptosis in skin cancer cells

Yuqin Hao,1 Xuefeng Bai,2 Xia Liu,1,3 Shuxia Kang,1,3 Xin Zhang,1,3 Caiyun Liu,4 Zhehai Li3,5 1Department of Dermatology, Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, 014010, People’s Republic of China; 2Department of Pathology, Baotou Cancer Hospital, Baotou, 014030, People’s Republic of China; 3Inner Mongolia Medical University, Hohhot, 010000, People’s Republic of China; 4Hunan Youcheng Biotechnology Co. Ltd, Changsha, 410000, People’s Republic of China; 5Department of Orthopedics, Beijing Northern Hospital, China North Industries, Beijing, 100089, People’s Republic of China Background: Survivin, a member of the inhibitor of apoptosis protein family, is highly expressed in many cancers and has important roles in inhibiting apoptosis by blocking caspase activation. However, its antitumor effects remain largely unknown. Here we explore the function of survivin in skin cancer. Methods: We used qPCR and Western blot to examine survivin expression in skin cancer patients and cell line. We generated several survivin shRNA constructs and tested the effects of survivin shRNA on cancer cell viability using MTT assay, flow cytometry, and TUNEL assay. Results: We found that survivin was upregulated in both skin cancer patients and skin cancer cell line A431. Knockdown survivin via shRNA inhibited cancer cell proliferation and promoted apoptosis in both A431 cell and in vivo xenograft tumor mouse model. The antitumor effect is comparable to resveratrol, a drug known to inhibit cancer progression. Moreover, we showed that inhibition of survivin was able to increase the expression of cleaved caspase 7/caspase 9 and activate the ataxia-telangiectasia mutated-NF-κB pathway in A431 cells. Conclusion: Survivin-shRNA possesses antitumor abilities in vitro and in vivo by inhibiting the proliferation and promoting apoptosis of A431 cells. It may serve as a potential anticancer target for skin cancer therapy in the future. Keywords: survivin, skin cancer, apoptosis, NF-κB, caspases 7/