[Experimental studies on anti-tumor effects of BLC-modified tumor cell vaccine combined with cisplatin].
OBJECTIVE
Chemokines are small molecule proteins that are the main mediators of cell migration. Studies indicated that chemokines could induce antitumor immune response strongly and steadily. At present, there was not antitumor therapy about chemokine BLC combined with chemotherapy. This study was designed to explore the anti-tumor effects and mechanisms of BLC-modified tumor cell vaccine combined with cisplatin.


METHODS
Firstly, we transfected pcDNA-BLC into murine tumor cell lines and established stable transfected tumor cell lines (Colon26 and LL/2) to express BLC. Null plasmid pcDNA3.1 (+) was also transfected into Colon 26 or LL/2 cells stably for comparison. We established mouse model with pcDNA-BLC stable transfected tumor cells (Tc), control mouse model with pcDNA3.1(+) stable transfected tumor cells (Pc), and mouse model with parental tumor cells (Nc). Then the 60 mice were inoculated subcutaneously (s.c.) in the right flanks with a total of 5x10(5) viable tumor cells (Tc to 20 mice, Pc to 20 mice, and Nc to 20 mice, respectively; 6-8 week BALB/c female mouse in colon 26 mouse model or 6-8 week C57BL/6 female mouse in LL/2 mouse model). The groups (Tc, Pc, and Nc) were randomly subdivided into Group A and Group B with 10 mice for each, resulting in Tc-A/Tc-B, Pc-A/Pc-B, and Nc-A/Nc-B, respectively. Group A (including Tc-A, Pc-A, and Nc-A) as chemotherapy group was injected (i.p.) with 0.1 ml cisplatin at the concentration of 2 mg/kg once a week for two weeks; Group B (including Tc-B, Pc-B, and Nc-B) as control with 0.1 normal saline. We further observed anti-tumor activity including the tumor growth, mice survival rate, side effects as well as tumor morphological analysis. Apoptotic cells were also determined in tumor tissues.


RESULTS
The combination therapy group Tc-A showed significant anticancer activities. The tumor growth was inhibited efficiently with 3/10 mice showing complete regression in LL/2 mouse model and 1/10 mice showing complete regression in Colon 26 mouse model. The combination therapy group Tc-A showed that the survival rate of mice was 100% in the two mouse models, compared with 68% in group Tc-B in C57BL/6 mouse model and 65% in group Tc-B in Colon 26 mouse model and those in other groups. In addition, the combination therapy group Tc-A induced tumor cell apoptosis significantly.


CONCLUSIONS
The therapy of BLC-modified tumor cell vaccine combined with cisplatin had significant synergistic effect against tumor. It might develop a new approach for specific immunotherapy of tumors.
Zou
Chun-Hua
CH
Key Laboratory of Biotherapy of Human Diseases, Ministry of Education,and Biotherapy and Research Center of Cancer,West China Hospital, Chengdu,Sichuan, 610041, P.R.China.
Tian
Ling
L
Wei
Yu-Quan
YQ
Zhao
Xia
X
Kan
Bing
B
Yang
Jin-Liang
JL
Mao
Yong-Qiu
YQ
Wen
Yan-Jun
YJ
Li
Jiong
J
Deng
Hong-Xin
HX
D000818:Animals; D017209:Apoptosis; D019496:Cancer Vaccines / Q000627:therapeutic use*; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000494:pharmacology*; D002945:Cisplatin / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*
D019496:Cancer Vaccines; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D002945:Cisplatin