The effects of irinotecan combined with 4-amion pyridine on the proliferation of human colorectal cancer cell
10.3760/cma.j.issn.0254-1432.2009.08.009
- VernacularTitle:伊立替康与4-氨基吡啶联合应用对人结直肠癌细胞增殖作用的影响
- Author:
Yining ZHANG
;
Minjie WEI
;
Mingjun SUN
- Publication Type:Journal Article
- Keywords:
Colorectal neoplasms;
Irinotecan;
4-aminopyridine;
ATP-sensitive potassium current
- From:
Chinese Journal of Digestion
2009;29(8):534-537
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and potential mechanism of irinotecan (CPT-11), an antitumor drug, on human colorectal cancer cell line HT-29 and its impact on 4-amion pyridine (4-AP), a kalium ion channel blocker. Methods The effects of CPT-11, 4-AP and combination of two drugs on proliferation and invasion of HT-29 cells were measured by MTT and Transwell assay respectively. The impact of CPT-11 or 4-AP on cell apoptosis was determined by flow cytometry with Annexin-V and PI staining. The current of ATP sensitive potassium ion (IKATP) was measured by patch clamp. Results The CPT-11 could inhibit proliferation of HT-29 cells at dose from 1.0 to 64.0 μg/ml in dose-and time-dependent manners. Whereas the above effect was enhanced when CPT-11 combined with 4-AP (1.0 mmol/L). The administration of CPT-11 (16.0 μg/ml) or 4-AP (1.0 mmol/L) significantly induced the cell apoptosis and inhibited the invasion of HT-29 cells, furthermore, these effects could be enhanced by combination of two drugs. And the different concentrations of CPT-11 reduced the IKATP of cell membrane in negative dose-dependent manner. Conclusions The effects of CPT-11 on HT-29 cells, such as reducing proliferation and invasion as well as inducing the apoptosis, can be enhanced by 4-AP, which may be related to inhibition of ATP-sensitive potassium channels.
