[Correlation of antitumor drug sensitivity between marrow mesenchymal stem cells (MSCs) and hepatocarcinoma cells in rats].
OBJECTIVE
As hepatocarcinoma stem cells may originate from oval cells and oval cells are difficult to be separated and purified, MSCs (marrow mesenchymal stem cells), which are the progenitor cells of the hepatocarcinoma stem cells, were selected instead in our study to investigate the correlation of anticancer drug sensitivity between hepatocarcinoma cells and MSCs in rats.


METHODS
The primary liver carcinoma modle of rats was induced by diethylnitrosamine. Tumor cells and MSCs from eight hepatocarcinoma rats were separated. The inhibitory effects of 3 anticancer drugs [adriacin (0.04 microg/ml), cisplatin (0.2 microg/ml) and fluorouracil (1 microg/ml)] to hepatocarcinoma cells and MSCs were measured by MTT assay. The weight of the tumor in nude mice which were injected with rat hepatocarcinoma cells was measured after 6 weeks. Then the correlation of the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and MSCs, and to the tumor weight of nude mice was analyzed.


RESULTS
No correlation was revealed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was: 0.6307 (adriacin, P>0.05), 0.4358 (fuiorouracil, P>0.05) and 0.7080 (cisplatin, P>0.05). No correlation was observed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and to MSCs. The correlation coefficient was: 0.6316 (adriacin, P>0.05), 0.4214 (fluorouracil, P>0.05) and 0.5943 (cisplatin, P>0.05). However, significant reverse correlation was found between the inhibitory ratio of 3 anticancer drugs to MSCs and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was: -0.8308 (adriacin, P<0.05), -0.8991 (fluorouracil, P<0.01) and -0.8311 (cisplatin, P<0.05).


CONCLUSIONS
Conventional anticancer drug sensitivity experiments could not reflect the chemoresistance of the hepatocarcinoma cells. However the inhibitory ratio of the anticancer drugs to MSCs in the hepatocarcinoma rats can reflect the chemoresistance of hepatocarcinoma cells accordingly.
Zhou
Si-Lang
SL
Department of Neoplasm, Zhujiang Hospital, The Southern Medical University, Guangzhou, 510282, P. R. China.
Li
Peng
P
Cao
Man-Ming
MM
Zhang
Ji-Ren
JR
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004052:Diethylnitrosamine; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005472:Fluorouracil / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004052:Diethylnitrosamine; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil