Guggulsterone of Commiphora mukul resin reverses drug resistance in imatinib-resistant leukemic cells by inhibiting cyclooxygenase-2 and P-glycoprotein

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• 作者：Hong-Bin Xu ; ^{xuhongbin@tongji.edu.cn" class="auth_mail} ; ^{xuhongbin119@yahoo.cn" class="auth_mail} ; Lu-Zhong Xu ; Xia-Ping Mao ; Jun Fu
• 关键词：Guggulsterone ; Commiphora mukul ; Imatinib resistant ; K562/IMA cells ; Cyclooxygenase-2 ; P-glycoprotein
• 刊名：Phytomedicine
• 出版年：15 June 2014
• 年：2014
• 卷：21
• 期：7
• 页码：1004-1009
• 全文大小：1267 K

文摘

The purpose of this study was to investigate the effects of guggulsterone on cyclooxygenase-2 and P-glycoprotein mediated drug resistance in imatinib-resistant K562 cells (K562/IMA). MTT cytotoxicity assay, flow cytometry, western blot analysis, and ELISA were performed to investigate the anti-proliferative effect, the reversal action of drug resistance, and the inhibitory effect on cyclooxygenase-2, P-glycoprotein, BCR/ABL kinase, and PGE₂ release in K562/IMA cells by guggulsterone. The results showed that co-administration of guggulsterone resulted in a significant increase in chemo-sensitivity of K562/IMA cells to imatinib, compared with imatinib treatment alone. Rhodamine123 accumulation in K562/IMA cells was significantly enhanced after incubation with guggulsterone (60, 120 渭M), compared with untreated K562/IMA cells (p < 0.05). When imatinib (1 渭M) was combined with guggulsterone (60, 120 渭M), the mean apoptotic population of K562/IMA cells was 15.47% and 24.91%. It was increased by 3.82 and 6.79 times, compared with imatinib (1 渭M) treatment alone. Furthermore, guggulsterone had significantly inhibitory effects on the levels of cyclooxygenase-2, P-glycoprotein and prostaglandin E₂. However, guggulsterone had little inhibitory effect on the activity of BCR/ABL kinase. The present study indicates guggulsterone induces apoptosis by inhibiting cyclooxygenase-2 and down-regulating P-glycoprotein expression in K562/IMA cells.