Pharmacological inhibition of protein kinase C activity could induce apoptosis in gastric cancer cells by differential regulation of apoptosis-related genes.
The protein kinase C (PKC) signaling pathway plays a key role in tumor cell proliferation, differentiation, and apoptosis. Gastric cancer usually possesses a higher level of PKC activity than normal tissue. We evaluated inhibition of PKC activity in apoptosis induction of gastric cancer cells and the expression profile of apoptosis-related genes. Gastric cancer cells (AGS) were incubated with two highly specific PKC inhibitors (RO-31-8220 and chelerythrine). Cell viability and cell cycle were determined by methyl-tetrazolium (MTT) assay and flow cytometry, respectively. Apoptosis was characterized by acridine orange staining, DNA gel electrophoresis, and flow cytometry. The expression of p53, p21(waf/cip1), c-myc, bcl-2, and bax was determined by western blot. The results showed that both PKC inhibitors hindered cell growth, arrested cells at G0/G1 phase and induced apoptosis. The protein level of p53, p21(waf/cip1), c-myc, and bax was elevated while bcl-2 kept unchanged following drug exposure. In conclusion, PKC inhibitors suppress growth of gastric cancer cells through apoptosis induction and cell cycle quiescence, which may be regulated by differential expression of apoptosis-related genes.
Zhu
G H
GH
Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong.
Wong
B C
BC
Eggo
M C
MC
Yuen
S T
ST
Lai
K C
KC
Lam
S K
SK
D000230:Adenocarcinoma / Q000473:pathology; D000470:Alkaloids; D017209:Apoptosis / Q000235:genetics*; D053119:Benzophenanthridines; D002453:Cell Cycle / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007211:Indoles; D010617:Phenanthridines; C016299:chelerythrine; D011493:Protein Kinase C; C064758:Ro 31-8220