Effect of sulindac derivative K-80003 in combination with MEK inhibitor cobimetinib in breast cancer cells / 中国药理学通报
Chinese Pharmacological Bulletin
;
(12): 251-254, 2019.
Article
in Chinese
| WPRIM
| ID: wpr-857292
ABSTRACT
Aim:
To determine whether the inhibition of K-80003-activated p-ERK could potentiate the anticancer effect of K-80003 in vitro and in vivo.Methods:
The effects of K-80003 in combination with the MEK inhibitor cobimetinib on ERK activation and tumor cell apoptosis in breast cancer cells were detected by Western blot and immunohistochemical staining in MCF-7 breast cancer cells and MMTV-PyMT mammary transgenic mice.Results:
K-80003 activation of ERK in MCF-7 breast cancer cells and in MMTV-PyMT mammary transgenic mice was strongly inhibited by co-treatment with cobimetinib. The co-treatment also resulted in a strong induction of apoptosis and inhibition of the growth of tumor cells in vitro and in animals, as compared with K-80003 alone. It was detected that K-80003 in combination with cobimetinib synergistically inhibited the growth of MMTV-PyMT tumor strongly, suggesting that K-80003 activation of ERK serves as an escape mechanism by which tumor cells develop resistance to K-80003 treatment.Conclusion:
An attractive approach is identified to enhance the therapeutic effect of K-80003 and to overcome potential resistance associated with the K-80003 therapy.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Chinese Pharmacological Bulletin
Year:
2019
Type:
Article
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