Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer.
Vesicular stomatitis virus (VSV) has been shown to replicate rapidly in vitro and kill selectively a variety of tumor cell lines. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro and in vivo. A549 human lung adenocarcinoma cells and LLC Lewis lung carcinoma cells were treated with VSV (0.1-10 plaque-forming units per cell) plus gemcitabine (20 nM to 20 microM). Mice bearing A549 or LLC were treated with VSV (5 x 10(4) to 1 x 10(8) plaque-forming units) daily for 5 days plus gemcitabine (5-125 mg/kg/day) once every 3 days for 4 times. Induction of apoptosis and effects on growth inhibition were assessed. The lung cancer cells treated with VSV plus gemcitabine displayed the apparently increased apoptotic cells compared with treatment with VSV or gemcitabine alone. The combined treatment with VSV plus gemcitabine induced the apparent antitumor activity with complete regression of the established lung cancer in both A549 and LLC lung cancer models and augmented the induction of apoptosis in lung cancer cells in vivo as well. This study suggests that the combined treatment with VSV plus gemcitabine may augment the induction of apoptosis in lung cancer cells in vitro and in vivo, and that the augmented antitumor activity in vivo may result from the increased induction of apoptosis in lung cancer cells. The present findings may be of importance to the further exploration of the potential application of this combined approach in the treatment of lung cancer.
Li
Qiu
Q
Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
Wei
Yu-Quan
YQ
Wen
Yan-Jun
YJ
Zhao
Xia
X
Tian
Ling
L
Yang
Li
L
Mao
Yong-Qiu
YQ
Kan
Bing
B
Wu
Yang
Y
Ding
Zhen-Yu
ZY
Deng
Hong-Xin
HX
Li
Jiong
J
Luo
Yan
Y
Li
Hong-Li
HL
He
Qiu-Ming
QM
Su
Jing-Mei
JM
Xiao
Fei
F
Zou
Chun-Hua
CH
Fu
Chun-Hua
CH
Xie
Xing-Jiang
XJ
Yi
Tao
T
Tan
Guang-Hong
GH
Wang
Lian
L
Chen
Jing
J
Liu
Jian
J
Gao
Zhen-Nan
ZN
D000230:Adenocarcinoma / Q000517:prevention & control / Q000821:virology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis; D018827:Carcinoma, Lewis Lung / Q000517:prevention & control / Q000821:virology; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000302:isolation & purification / Q000502:physiology*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine