[Reversing multidrug resistance of epidermoid carcinoma drug-resistant cell line KB-MRP1 by tetrandrine].
OBJECTIVE
Tetrandrine (Tet), a bisbenzylisoquinoline albaloid isolated from the Chinese herb "Hanfangji" (Radix Stephania Tetrandra), could effectively reverse P-glycoprotein-mediated multidrug resistance. This study was to investigate the reversal effect of tetrandrine on multidrug resistance of human epidermoid carcinoma cell line KB-MRP1.


METHODS
The effects of tetrandrine on the proliferation of KB-3-1 and KB-MRP1 cells were observed by MTT assay. The inhibitory effects of cisplatin (DDP), vincristine (VCR), adriamycin (ADM) and etoposide (VP-16) used alone or in combination with tetrandrine on the proliferation of KB-3-1 and KB-MRP1 cells were evaluated by MTT assay. The effects of tetrandrine on ADM accmulation in KB-MRP1 cells and VCR-induced apoptosis were determined by flow cytometry (FCM).


RESULTS
Tetrandrine at the concentration of 1.5 microg/ml and below showed no significant cytotoxicity to KB-3-1 and KB-MRP1 cells. The resistance of KB-MRP1 cells to VCR, ADM, VP-16 and DDP were 21.23, 38.39, 12.47 and 1.31 folds of that of KB-3-1 cells. When added 1 microg/ml tetrandrine, the chemosensitivity of KB-MRP1 cells to VCR, ADM and VP-16 were increased to 4.96, 5.85 and 4.24 folds, respectively; when added 1.5 microg/ml tetrandrine, the chemosensitivity of KB-MRP1 cells to VCR, ADM and VP-16 were much higher. When treated with 1.5 microg/ml tetrandrine, ADM accumulation in KB-MRP1 cells and the VCR-induced apoptosis were enhanced significantly.


CONCLUSIONS
Tetrandrine could moderately reverse the multidrug resistance of KB-MRP1 cells through increasing the accumulation of chemo-drugs in cells and promoting apoptosis.
Chen
Xiao-Song
XS
Department of Respiratory Medicine, Affiliated Provincial Hospital, Anhui Medical University, Hefei, Anhui, 230001, PR China.
Bao
Ming-Hong
MH
Mei
Xiao-Dong
XD
D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007624:KB Cells; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D002945:Cisplatin; D004317:Doxorubicin; D005047:Etoposide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014750:Vincristine; C009438:tetrandrine; C421109:multidrug resistance-associated protein 1