Cross-reacting material 197 reverses the resistance to paclitaxel in paclitaxel-resistant human ovarian cancer
Cross-reacting material 197 reverses the resistance to paclitaxel in paclitaxel-resistant human ovarian cancer
复制标题
交叉反应物质197逆转紫杉醇耐药的人卵巢癌对紫杉醇的耐药性
DOI：
10.1007/s13277-015-4412-0
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Lu Mei song
中科院分区：
文献类型：
--
作者：
Tang Xiao han;Deng Suo;Li Meng;Lu Mei song
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been proven to be a promising chemotherapeutic target for ovarian cancer. Our previous studies have demonstrated that inhibition of HB-EGF by the special inhibitor, cross-reacting material 197 (CRM197), potently inhibits the anti-tumor activity in paclitaxel-resistant ovarian cancer. Here, we found that inhibition of HB-EGF by CRM197 significantly reverses the resistance to paclitaxel in paclitaxel-resistant ovarian carcinoma cell line (A2780/Taxol). A2780/Taxol cells over-expressed HB-EGF and epidermal growth factor receptor (EGFR) and CRM197 notably suppressed the expression of HB-EGF and EGFR. Experiments performed in vitro and in vivo further suggested that CRM197 markedly down-regulated the ATP-binding cassette sub-family B member 1 (ABCB1/MDR1) messenger RNA (mRNA) expression (P= 0.01), plasma membrane glycoprotein (P-gp) protein (P= 0.009), and P-gp-mediated efflux (P= 0.007) through inhibition of nuclear factor-κB (NF-κB) expression, which were classical chemoresistance-related targets with respect to paclitaxel therapy. Meanwhile, inhibition of HB-EGF enhanced caspase-3 activity to induce apoptosis via MDR1 inhibition in A2780/Taxol cells (P= 0.038). Collectively, HB-EGF is a molecular target for the resistance of ovarian cancer to paclitaxel and CRM197 as a HB-EGF-targeted agent might be a chemosensitizing agent for paclitaxel-resistant ovarian carcinoma. Our findings provide novel possible mechanisms for HB-EGF to be a target to restore the chemosensitivity to paclitaxel.
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影响因子：
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