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Baicalin-induced Cytotoxicity and Apoptosis in Multidrug-resistant MC3/5FU Mucoepidermoid Carcinoma Cell Line

[ Vol. 16 , Issue. 12 ]

Author(s):

Xiaofang Xu, Qihong Li, Kaitao Yu*, Ghulam Murtaza* and Bin Liu*   Pages 1339 - 1347 ( 9 )

Abstract:


Background: Multidrug Resistance (MDR) is a serious hindrance to cancer chemotherapy and profoundly influences the clinical findings. Many Traditional Chinese Medicines (TCM) have been tested with the aim of developing effective resistance modulators or anticancer drugs to overcome the MDR of human cancers.

Methods: The anticancer effect of baicalin on multidrug-resistant MC3/5FU (5-fluorouracil) cells was investigated by MTT test and xenografts in nude mice. Cell apoptosis was studied by transmission electron microscopy, Hoechst-33342 staining, DNA fragmentation detection, and flow cytometry. RT-PCR and Rhodamine 123 efflux assay was also used to detect its effect on ABC drug transporter proteins, ABCB1 (P-glycoprotein, P-gp) and ABCC1 (multidrug resistance protein 1, MRP1).

Results: The results indicate that there was no significant effect of baicalin on ABC transporters expression or efflux function, although it induced potent growth inhibition in MC3/5FU cells. Flow cytometry, Hoechst 33342 staining and transmission electron microscope revealed that baicalin caused MC3/5FU cell death through the induction of apoptosis. It is demonstrated that baicalininduced apoptosis could be mediated by up-regulation of Bax and caspase-3 protein levels and downregulation of Bcl-2 protein levels. In addition, daily intraperitoneal injection of baicalin (100 and 200 mg/kg) for 2 weeks significantly inhibited the growth of MC3/5FU cells xenografts in nude mice.

Conclusion: Our results suggest that baicalin possesses considerable cytotoxic activity in multidrug resistance MC3/5FU cells in vitro and in vivo.

Keywords:

Baicalin, mucoepidermoid carcinoma, multidrug resistance, bcl-2, bax, apoptosis, xenografts.

Affiliation:

Department of Stomatology, Affiliated Hospital of the Academy of Military Medical Sciences, Beijing 100071, Department of Stomatology, Affiliated Hospital of the Academy of Military Medical Sciences, Beijing 100071, Department of Stomatology, Affiliated Hospital of the Academy of Military Medical Sciences, Beijing 100071, Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, The Fourth Military Medical University, 145th West Changle Road, Xi'an 710032

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