Acetyltanshinone IIA is more potent than lapatinib in inhibiting cell growth and degrading HER2 protein in drug-resistant HER2-positive breast cancer cells

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	Acetyltanshinone IIA is more potent than lapatinib in inhibiting cell growth and degrading HER2 protein in drug-resistant HER2-positive breast cancer cells
	Huang, B; Yip, WK; Na, W; Luo, KQ
	2020-06-23
Source Publication	Cancer Letters
ISSN	0304-3835
Pages	1-11
Abstract	High expression of human epidermal factor receptor 2 (HER2) is directly related to tumor progression, malignancy and drug resistance in HER2-positive breast cancer (HER2-PBC). The major limitation of current anti-HER2 therapies is that they cannot reduce the levels of HER2 protein. Here, we investigated the effect of acetyltanshinone IIA (ATA) in lapatinib-resistant HER2-PBC cells. Our data showed that ATA exhibited more potent effects than lapatinib against drug-resistant HER2-PBC cells in terms of (1) inhibiting cell growth, (2) reducing phosphorylated and total HER2 levels, (3) inhibiting tumor xenograft growth in nude mice, and (4) reducing HER2 protein levels in tumor xenografts. A mechanistic study revealed that ATA promoted HER2 degradation via increasing c-Cbl and CHIP-mediated HER2 ubiquitination and subsequent HER2 degradation by the proteasome or lysosome. ATA also reduced the levels of other tyrosine kinase receptors (TKRs), such as HER3, IGF-1R and MET, in lapatinib-resistant cells. Our findings suggest that direct degradation of HER2 and other TKRs can be an effective strategy for combatting drug resistance. They also indicate the potential utilization of ATA in treating breast cancer that is resistant or nonresponsive to current HER2-targeted therapies.
Keyword	Acetyltanshinone IIA drug resistance HER2-positive breast cancer HER2 degradation
Language	英語English
The Source to Article	PB_Publication
PUB ID	37589
Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	Luo, KQ
Recommended Citation GB/T 7714	Huang, B,Yip, WK,Na, W,et al. Acetyltanshinone IIA is more potent than lapatinib in inhibiting cell growth and degrading HER2 protein in drug-resistant HER2-positive breast cancer cells[J]. Cancer Letters, 2020, 1-11.
APA	Huang, B., Yip, WK., Na, W., & Luo, KQ (2020). Acetyltanshinone IIA is more potent than lapatinib in inhibiting cell growth and degrading HER2 protein in drug-resistant HER2-positive breast cancer cells. Cancer Letters, 1-11.
MLA	Huang, B,et al."Acetyltanshinone IIA is more potent than lapatinib in inhibiting cell growth and degrading HER2 protein in drug-resistant HER2-positive breast cancer cells".Cancer Letters (2020):1-11.

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