Efficient inhibition of cisplatin-resistant human ovarian cancer growth and prolonged survival by gene transferred vesicular stomatitis virus matrix protein in nude mice.
BACKGROUND
The vesicular stomatitis virus matrix protein (VSVMP) has been receiving attention as an anticancer agent because of its ability of inducing apoptosis.


METHODS
Nude mice bearing A2780s and A2780cp ovarian tumors were treated twice weekly with i.v. administration of 50 microg VSVMP/250 mug liposome complex, 50 microg empty plasmid/250 microg liposome complex, 0.9% NaCl solution or weekly with i.p. administration of cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. TUNEL assay and CD34 vessel staining were conducted in tumor tissue. Antiangiogenesis in vivo were determined by sponge assay. Antiproliferative and apoptosis-inducing activities of VSVMP in vitro were tested on MS1 murine endothelial cells and four human ovarian cancer cell lines: A2780s, A2780cp, HO8910 and COC1.


RESULTS
Administration of VSVMP resulted in significant inhibition (87%-98% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts, and prolonged the survival of the treated mice. Complete tumor regression happened in VSVMP-treated mice in both tumor models. These antitumor responses were associated with marked increases in tumor apoptosis and reductions in intratumoral microvessel density.


CONCLUSIONS
Our data indicate that VSVMP may provide an effective approach to inhibit both cisplatin-sensitive and -resistant human ovarian cancer growth with minimal side-effects.
Zhong
Q
Q
Department of Gynecology and Obstetrics, West China Second Hospital and State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, China.
Wen
Y-J
YJ
Yang
H-S
HS
Luo
H
H
Fu
A-F
AF
Yang
F
F
Chen
L-J
LJ
Chen
X
X
Qi
X-R
XR
Lin
H-G
HG
Wan
Y
Y
Chen
X-C
XC
Wei
Y-Q
YQ
Zhao
X
X
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D018116:Vesiculovirus; D014763:Viral Matrix Proteins / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D014763:Viral Matrix Proteins; D002945:Cisplatin