Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamous cell carcinoma.
Despite advances in surgery, radiotherapy, and chemotherapy, the long-term survival rates with oral squamous cell carcinoma (OSCC) have not significantly improved. Gene therapy for OSCC is currently under investigation in clinical trials. Lentivirus vector is considered to be a promising gene delivery tool, but their value in cancer gene therapy has not been studied thoroughly. Survivin is overexpressed in OSCC, making it a promising target for gene therapy. This study was conducted to determine whether lentivirus-mediated gene therapy by suppressing survivin could be exploited in the treatment of OSCC. A lentivirus vector encoding short hairpin RNA (shRNA) targeting survivin was constructed and transfected into KB cells in vitro. The results showed that survivin was persistently and markedly reduced by lentivirus-mediated RNA interference (RNAi); the growth of KB cells was decreased by 34.2% on day 5; the apoptosis rate induced by vincristine (VCR) was increased by 29.8% and caspase-3 activity was also significantly increased; the IC(50) value of adriamycin (ADM) were 0.09 mug/ml, which indicated that survivin-knockout KB cells were 2.1 times more susceptible to ADM than the control; the clonogenic survival rate at 6 Gy of X ray was 3.7%, less than 15.3% of the control. In the xenograft model, the development of tumors as well as the growth of established tumors was inhibited by transfection of lentivirus. Our study indicates that lentivirus-mediated gene therapy is an attractive strategy in the treatment of OSCC and justifies the use of lentivirus in cancer gene therapy studies.
Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Gaofeng
G
Jiang
Jinlong
J
Li
Zhaolei
Z
Zeng
Lijian
L
Xian
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000628:therapy*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics*; D034622:RNA Interference; D012097:Repressor Proteins; D000077022:Survivin
C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; D000077022:Survivin; D053148:Caspase 3