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.
Jiang
Gaofeng
G
Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Li
Jinlong
J
Zeng
Zhaolei
Z
Xian
Lijian
L
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