[Growth inhibition of human hepatocellular carcinoma xenograft in nude mice by combined treatment with human cytokine-induced killer cells and chemotherapy].
OBJECTIVE
To compare the inhibitory effects of cytokine-induced killer (CIK) cells alone, chemotherapeutic drug alone, and CIK cells combined with chemotherapeutic drug on the growth of hepatocellular carcinoma (HCC) cells transplanted in nude mice.


METHODS
Peripheral blood mononuclear cells (PBMC) collected from five healthy donors by blood cell separator were incubated in vitro to induce CIK cells in the presence of interferon-gamma (IFN-gamma), IL-2 and anti-CD3 monoclonal antibody (mAb). The phenotype of CIK cells was characterized by flow cytometric analysis. BEL-7402 HCC cells were inoculated subcutaneously to nude mice. On day 5, at the inoculation site were injected normal saline (group 1), CIK cells (3 x 10(7) and 6 x 10(7), group 2 and 3), mitomycin-C (MMC 80 microg in 0.2 ml, group 4), and CIK cells combined with MMC (group 5), respectively.


RESULTS
The percentage of CD3(+), CD3(+)CD8(+), CD3(+)CD56(+), CD25(+) cells increased from 64.0%, 28.0%, 7.8%, and 9.1% to 94.7%, 67.7%, 61.3%, and 84.0% respectively after cytokine induction. The percentage of CD3(+) and CD3(+)CD8(+) cells remained at high levels during incubation period, but that of CD25(+) and CD3(+)CD56(+) cells peaked respectively on day 7 and 13 and then declined. During the 90-day observation, the tumor formation rates were 100%, 70.0%, 80.0%, 70.0% and 66.7%; and the mouse survival rates were 10.0%, 60.0%, 40.0%, 50.0% and 75.0%, respectively from group 1 to group 5. Compared to the other groups, in the combined therapy group of mice, not only the tumor grew slowly and but also showed more marked tissue necrosis.


CONCLUSIONS
The growth inhibitory effect on human HCC transplanted in nude mice of combined CIK cells and MMC treatment is more potent than that of CIK cells or MMC alone.
Shi
Ming
M
Division of Biological Engineering, Beijing Institute of Infectious Disease, the 302 Hospital of PLA, Beijing 100039, China.
Yao
Li
L
Wang
Fu-Sheng
FS
Lei
Zhou-Yun
ZY
Zhang
Bing
B
Li
Wen-Liang
WL
Liu
Jing-Chao
JC
Tang
Zi-Rong
ZR
Zhou
Guang-de
GD
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000637:transplantation*; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use*; D009368:Neoplasm Transplantation
D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D016685:Mitomycin