Antitumor effect of the integrin alpha 4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells

作者：Thien Nhan Lu; Ganganna Bogonda; Thuy Trang Pham; Anh Van Vo; Thien Phuc Lu; Huong Giang Thi Nguyen; My Nuong Thi Nguyen; Phuong Nguyen Huynh; Ngoc Tuyen Truong; Lee Jongkook

来源：Biochemical and Biophysical Research Communications, 2017, 491(2): 355-360.

DOI：10.1016/j.bbrc.2017.07.096

• JK273
• Non-small cell lung cancer
• NSCLC
• NCI-H460
• Integrin
• Anti-tumor

Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits alpha 4 integrin signaling, showed a selective cytotoxic effect against HCl-H460 NSCLC cells, with an IC50 of 0.98 +/- 0.15 mu M, but showed less sensitivity to fibroblasts with a selectivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes. Taken together with the previous study of JK273 inhibiting cell migration, we propose that JK273 could serve as an antitumor compound to specifically target cancer cells but not non-cancerous cells by triggering programmed cell death, in addition to anti metastatic effects in cancer therapy.

• 出版日期2017-9-16