THE ROLE OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN THE FORMATION OF ADRIAMYCININDUCED MULTIDRUG RESISTANCE TO HEPATOCELLULAR CANCER CELL SMMC-7721 IN HUMAN HEPATOCELLULAR CARCINOMA_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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Department of General Surgery, First Affiliated Hospital, West China University of Medical Sciences, Chengdu 610041;

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Hepatocellular carcinoma Adriamycin Multidrug resistance-associated protein

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Objective To dynamically study the formation of multidrug resistance(MDR) of human hepatocellular carcinoma cell SMMC-7721 induced by Adriamycin (ADM) and the role of multidrug resistance-associated protein(MRP) in its mechanisms.
Methods Hepatocellular carcinoma cell SMMC-7721 was cultured in RPMI-1640 medium containing ADM with progressively increased concentration or directly cultured in medium containing different concentrations of ADM. Resistant index of drug-resistant variants of SMMC-7721 cell was determined by drawing cell dosage-reaction curves.Levels of MRP mRNA expression were detected by reverse transcription-polymerase chain reaction(RTPCR). Intracellular rubidomycin(DNR) concentration was examined by flow cytometry(FCM).
Results With progressive increasing of ADM concentration in medium resistant index and levels of MRP mRNA expression were correspondingly increased but intracellular DNR concentration was markly reduced. When parental cells were directly cultured in medium containing different concentrations of ADM, the higher the ADM concentration, the higher the level of MRP mRNA expression, but intracellular DNR concentration was kept at the similar high level and most cells died.
Conclusion ADM may progressively induce SMMC-7721 cell resistant to multiple chemotherapeutic drugs with reduced intracellular DNR accumulation associated with the overexpression of MRP gene.

Citation： DAI Yuemeng,LIN Qiyuan,YAN Lnan,et al.. THE ROLE OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN THE FORMATION OF ADRIAMYCININDUCED MULTIDRUG RESISTANCE TO HEPATOCELLULAR CANCER CELL SMMC-7721 IN HUMAN HEPATOCELLULAR CARCINOMA. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2001, 8(1): 8-11. doi: Copy

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1. Beck WT. The cell biology of multiple drug resistance[J]. Biochem Pharmac, 1987; 36(18)∶2879.
2. Barrand MA, HeppellParton AC, Wright KA, et al. A 190kilodalton protein overexpressed in nonPglycoproteincontaining multidrugresistant cells and is relationship to the MRP gene[J]. J Natl Cancer Inst, 1994; 86(2)∶110.
3. Paul S, Belinsky MG, Shen H, et al. Structure and in vitro substrate specificity of the murine multidrug resistantassociated protein [J]. Biochem, 1996; 35(42)∶13647.
4. Krishnamachary N, Center MS. The MRP gene associated with a nonpglycoprotein multidrug resistance encodes a 190KDa membrane bound glycoprotein [J]. Cancer Res, 1993; 53(16)∶3658.
5. Cole SCP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrugresistant human lung cancer cell line [J]. Science, 1992; 258(5088)∶1650.
6. Endo K, Maehara Y, Kusumoto T, et al. Expression of multidrugresistanceassociated protein(MRP) and chemosensitivity in human gastric cancer [J]. Int J Cancer, 1996; 68(3)∶372.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

THE ROLE OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN THE FORMATION OF ADRIAMYCININDUCED MULTIDRUG RESISTANCE TO HEPATOCELLULAR CANCER CELL SMMC-7721 IN HUMAN HEPATOCELLULAR CARCINOMA

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