拉帕蒂尼
蛋白酶体抑制剂
MG132型
蛋白酶体
硼替佐米
癌症研究
ErbB公司
乳腺癌
Hsp90抑制剂
乳酰丝汀
热休克蛋白90
药理学
癌症
医学
热休克蛋白
生物
内科学
曲妥珠单抗
生物化学
多发性骨髓瘤
基因
作者
Thanh Kieu Huynh,Chien Yi Ho,Chi Hua Tsai,Chien-Kuo Wang,Yun Ju Chen,Da Tian Bau,Chih Yen Tu,Tzong Shiun Li,Wei‐Chien Huang
摘要
Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors.
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