Zhi-Yuan Li1, Zhen-Jie Li2, Xu Chen3, Xing-Ru Huang3, Zhi-Qing Fang3, Jian-Guo Zhang3, Jian Fang4. 1. Department of Orthopaedics, Guangzhou Orthopedic Hospital, Guangzhou 510045, Guangdong Province, China. 2. Department of Orthopaedics, Guangzhou City Liwan District Orthopedic Hospital, Guangzhou 510140, Guangdong Province, China. 3. Department of Orthopaedics, Third Clinical Medical College of Guangdong University of Traditional Chinese Medicine, Guangzhou 510000, Guangdong Province, China. 4. Department of Orthopaedics, Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510240, Guangdong Province, China. E-mail: fangjian@gzucm.edu.cn.
Abstract
OBJECTIVE: To investigate the reversing effect of icaritin on multidrug resistance of multiple myeloma cell lines KM3/BTZ and its underlying mechanism. METHODS: KM3/BTZ cells were established by a gradually ascending gradient induction of bortezomib (BTZ). The sensitivities of KM3 and KM3/BTZ cells to 7 chemotherapeutic drugs, the inhibition and reversal effects of icaritin on proliferation and drug-resistance of KM3/BTZ cells were analyzed by MTT. The apoptosis was analyzed by flow cytometry, and the expression of Par-4, HSP27 and P-gp were detected by Western blot. RESULTS: KM3/BTZ cells were not only resistant to BTZ, but also to other 6 chemotherapeutic drugs. The resistance index (RI) to BTZ was 17.84, and higher than that of other chemotherapeutic drugs. Icaritin inhibited the proliferation and induced the apoptosis of KM3/BTZ cells. The IC50 value of BTZ decreased from 0.345 µg/ml to 0.149 µg/ml, and the reversal index was 2.38 (P<0.05). The expression of Par-4 protein increased in a concentration-dependent manner, while the expression of HSP27 and P-gp were down-regulated. CONCLUSION: Icaritin can inhibit cell proliferation and induce apoptosis of KM3/BTZ cells, moreover, can effectively reverse the multidrug resistance of KM3/BTZ cells. The mechanism may be related with down-regulation of HSP27 and P-gp expression, and up-regulation of Par-4 expression.
OBJECTIVE: To investigate the reversing effect of icaritin on multidrug resistance of multiple myeloma cell lines KM3/BTZ and its underlying mechanism. METHODS: KM3/BTZ cells were established by a gradually ascending gradient induction of bortezomib (BTZ). The sensitivities of KM3 and KM3/BTZ cells to 7 chemotherapeutic drugs, the inhibition and reversal effects of icaritin on proliferation and drug-resistance of KM3/BTZ cells were analyzed by MTT. The apoptosis was analyzed by flow cytometry, and the expression of Par-4, HSP27 and P-gp were detected by Western blot. RESULTS: KM3/BTZ cells were not only resistant to BTZ, but also to other 6 chemotherapeutic drugs. The resistance index (RI) to BTZ was 17.84, and higher than that of other chemotherapeutic drugs. Icaritin inhibited the proliferation and induced the apoptosis of KM3/BTZ cells. The IC50 value of BTZ decreased from 0.345 µg/ml to 0.149 µg/ml, and the reversal index was 2.38 (P<0.05). The expression of Par-4 protein increased in a concentration-dependent manner, while the expression of HSP27 and P-gp were down-regulated. CONCLUSION:Icaritin can inhibit cell proliferation and induce apoptosis of KM3/BTZ cells, moreover, can effectively reverse the multidrug resistance of KM3/BTZ cells. The mechanism may be related with down-regulation of HSP27 and P-gp expression, and up-regulation of Par-4 expression.