[Establishment of in vivo adriamycin-induced multidrug resistance models of subcutaneous and hepatic transplanted human liver cancer in nude mice].
OBJECTIVE
Multidrug resistance (MDR) phenotype is the obstacle of chemotherapy in tumors and inspired research interesting. This study was to establish multidrug resistance (MDR) models induced with adriamycin in vivo of subcutaneous or in situ hepatic transplanted human liver cancer in nude mice (BALB/C nu/nu), and explore the biological characteristics and mechanism of multidrug resistance, which can provide an ideal animal model for the basic,and clinical study of MDR.


METHODS
After successful performing either subcutaneous or hepatic transplantation in nude mice with liver cancer cell line HepG2, adriamycin (ADM) was injected into abdominal cavity to induce multidrug resistance. The chemosensitivity of HepG2 and ADM-cultured HepG2 cells was determined by MTT assay. P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), and cell pump-efflux to Rhodamine 123 (R123) were determined by flow cytometry. The mRNA expression of P-gp, MRP, and LRP was assessed with reverse transcriptase polymerase chain reaction(RT-PCR).


RESULTS
Most biological characteristics of either subcutaneous or hepatic transplanted HepG2 liver cancer in nude mice like the parent HepG2 liver cancer. Both of them showed significant multidrug resistance. Among them, the resistance index of ADM was 26.4 times in hepatic transplanted group, and 24.6 times in subcutaneous transplanted group higher than that of parent cell line HepG2. In subcutaneous,and hepatic transplanted ADM-cultured groups, P-gp [(77.3+/-2.1)%, and (78.1+/-1.9)%], MRP [(72.1+/-4.3)%, and (72.7+/-5.0)%], and LRP [(31.1+/-1.0)%, and (32.2+/-1.4)%] positive cells increased significantly, their mRNA positive expression increased also, and the cell pump-efflux to R123 strengthened. However, no significant difference of above data was observed between subcutaneous,and hepatic transplanted tumor group (P >0.05).


CONCLUSIONS
Both MDR subcutaneous and hepatic HepG2 transplanted models induced by in vivo injection of adriamycin in nude mice have the same biological characteristics as parent HepG2 liver cancer. These 2 animal models could be used as in vivo MDR models to explore the mechanism of MDR and reversing therapeutic methods.
Department of Biomedical Engineering, Institute of Ultrasound and Engineering in Medicine, Chongqing University of Medical Science, Chongqing, 400016, PR China. zhaibaojin@yahoo.com.cn
Bao-Jin
BJ
Zhai
Feng
F
Wu
Ze-Yong
ZY
Shao
Kai
K
Hu
Chun-Liang
CL
Zhao
Zhi-Biao
ZB
Wang
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis / Q000235:genetics; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein