Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice.
OBJECTIVE
To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT.


METHODS
Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay.


RESULTS
The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F = 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (chi2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups.


CONCLUSIONS
ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.
Zheng
Min-Hua
MH
Department of General Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Feng
Bo
B
Li
Jian-Wen
JW
Lu
Ai-Guo
AG
Wang
Ming-Liang
ML
Hu
Wei-Guo
WG
Sun
Ji-Yuan
JY
Hu
Yan-Yan
YY
Ma
Jun-Jun
JJ
Yu
Bao-Ming
BM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004599:Electric Stimulation Therapy / Q000379:methods*; D018274:Electroporation / Q000379:methods*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin