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[Delayed rectifier K(+) channel regulated by cyclooxygenase-2 in human gastric cancer cell]
Hanping Wu1, Kaichun Wu, Ying Han
1Department of Gastroenterology, Institute of Digestive Diseases, Xijing Hospital, Xi'an 710032, China.
Objective:
To correlate delayed rectifier K(+) channel to cyclooxygenase-2 (COX-2) in onco genesis of human gastric cancer cell.
Methods:
Human COX-2 encoding gene was cloned with RT-PCR strategy and its antisense recombinant eukaryotic expression vector was constructed. COX-2 highly expressed human gastric cancer cell line SGC7901 was stably transfected with the antisense vector. The whole-cell recording technique of perforated patch clamp was employed to observe the change of delayed rectifier K(+) current (I(k)) of SGC7901 after gene transfer or treatment with COX-2 inhibitor indomethacin. MTT was also performed to determine the effect of delayed rectifier K(+) channel inhibitors on cell growth.
Results:
Stably transfected cell (7901-AS) was obtained and a down-regulated expression of COX-2 protein and mRNA in the cell was achieved. Patch clamp recording showed that both SGC7901 and 7901-AS cells had a typical delayed rectifier K(+) current. However, I(k) was significantly lower (P < 0.01) in transfected cell or cell treated with indomethacin at each test potential. The altered I(k) could be entirely recovered after drug removal from the cells. K(+) channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) could retard the growth of SGC7901 and the transfected cell in a dose-dependent manner.
Conclusion:
Delayed rectifier K(+) channel, existing in human gastric cancer cell line SGC7901, is related to the growth of the cell. The highly expressed COX-2 may affect the biological behavior of gastric cancer cell by regulating this ion channel.
Insights
Delayed rectifier potassium channels are linked to gastric cancer growth. Inhibiting cyclooxygenase-2 (COX-2) reduces these channels, impacting cancer cell proliferation.
Area of Science:
- Molecular Biology
- Oncology
- Ion Channel Physiology
Context:
- Gastric cancer is a significant global health concern with complex underlying molecular mechanisms.
- Cyclooxygenase-2 (COX-2) is frequently overexpressed in gastric cancer and implicated in tumorigenesis.
- Ion channels play crucial roles in cell function, including proliferation and survival.
Purpose:
- To investigate the relationship between the delayed rectifier potassium channel and cyclooxygenase-2 (COX-2) in human gastric cancer.
- To determine if modulating COX-2 expression or activity affects delayed rectifier potassium channel function.
- To assess the impact of targeting this ion channel on gastric cancer cell growth.
Summary:
- Human gastric cancer cells (SGC7901) were engineered to downregulate COX-2 expression using an antisense vector.
- Patch clamp electrophysiology revealed significantly reduced delayed rectifier potassium current (I(k)) in COX-2 downregulated cells or cells treated with the COX-2 inhibitor indomethacin.
- Potassium channel blockers demonstrated a dose-dependent inhibition of both normal and transfected gastric cancer cell growth.
Impact:
- This study establishes a correlation between the delayed rectifier potassium channel and gastric cancer cell proliferation.
- Findings suggest that highly expressed COX-2 may influence gastric cancer cell behavior by regulating this specific ion channel.
- The results highlight potential therapeutic avenues targeting ion channel function in gastric cancer treatment.