Induction of apoptosis by arsenic trioxide and hydroxycamptothecin in gastric cancer cells in vitro

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:linfenrir
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AIM To study the effects of arsenic trioxide andHCPT on different degrees of differentiated gastriccancer cells(SGC-7901,MKN-45,MKN-28)withrespect to both cytotoxicity and induction ofapoptosis in vitro.METHODS The cytotoxicity of As_2O_3 and HCPTon gastric cancer cells was determined by MTTassay.Morphologic changes of apoptosis ofgastric cancer cells were observed by lightmicroscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancercells induced by HCPT and As_2O_3 were investigatedby TUNEL method and flow cytometry.RESULTS As_2O_3 and HCPT had remarkablecytotoxic effects on different degrees ofdifferentiated gastric cancer cells.The IC_(50)ofAs_2O_3 on well differentiated gastric cancer cellMKN-28,moderately differentiated gastric cancercell SGC-7901,and poorly differentiated gastriccancer cell MKN-28 were 8.91 μmol/L,10.57μmol/L,and 11.65 μmol/L,respectively.The IC_(50)of HCPT on MKN-28,SGC-7901,and MKN-45 were9.35 mg/L,10.21 mg/L,and 12.63 mg/Lrespectively after 48 h treatment.After 12 h ofexposure to both drugs,gastric cancer cellsexhibited morphologic features of apoptosis,including cell shrinkage,nuclear condensation, and formation of apoptotic bodies.A typicalsubdiploid peak before G_0/G_1 phase was observedby flow cytometry.The apoptotic rates of SGC-7901,MKN-45,and MKN-28 were 13.84%,22.52%,and 9.68%,respectively after 48 hexposure to 10 μmol/L As_2O_3.The apoptotic ratesof SGC-7901,MKN-45,and MKN-28 were 21.88%,12.35%,and 30.26%,respectively after 48 hexposure to 10 mg/L HCPT.The apoptotic indicewere 7%-15% as assessed by TUNEL method.The effect of As_2O_3 on SGC-7901 showedremarkable cell cycle specificity,which inducedcell death in G_1 phase,and blocked G_2/M phase.HCPT also showed a remarkable cell cyclespecificity,by inducing cell death and apoptosis inG_1 phase and arrest of proliferation at S phase.CONCLUSION As_2O_3 and HCPT exhibitsignificant cytotoxicity on gastric cancer cells byinduction of apoptosis.As_2O_3 and HCPT mighthave a promising prospect in the treatment ofgastric cancer,which needs to be further studied. AIM To study the effects of arsenic trioxide andHCPT on different degrees of differentiated gastriccancer cells(SGC-7901,MKN-45,MKN-28)withrespect to both cytotoxicity and induction ofapoptosis in vitro.METHODS The cytotoxicity of As_2O_3 and HCPTon gastric cancer cells was Determined by MTTassay. Morphologic changes of apoptosis ofgastric cancer cells were observed by lightmicroscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancercells induced by HCPT and As_2O_3 were investigatedby TUNEL method and flow cytometry.RESULTS As_2O_3 and HCPT had relevantcytotoxic effects on different The degree of differentiated gastric cancer cells. The IC_(50) ofAs_2O_3 on well differentiated gastric cancer cell MKN-28, moderately differentiated gastric cancercell SGC-7901, and poorly differentiated gastriccancer cell MKN-28 were 8.91 μmol/L, 10.57μmol/L, and 11.65. Μmol/L, respectively. The IC_(50) of HCPT on MKN-28, SGC-7901, and MKN-45 were 9.35 mg/L, 10.21 mg/L, and 12.63 mg After 48 hours of treatment,After 12 h ofexposure to both drugs,gastric cancer cells exhibited morphologic features of apoptosis,including cell shrinkage,nuclear condensation, and formation of apoptotic bodies.A typical subdiploid peak before G_0/G_1 phase was observed by flow cytometry.The Apoptotic rates of SGC-7901, MKN-45, and MKN-28 were 13.84%, 22.52%, and 9.68%, respectively after 48 hexposure to 10 μmol/L As_2O_3. The apoptotic ratesof SGC-7901, MKN-45, and MKN -28 were 21.88%, 12.35%, and 30.26%, respectively after 48 hexposure to 10 mg/L HCPT.The apoptotic indicewere 7%-15% as assessed by TUNEL method.The effect of As_2O_3 on SGC-7901 was shown by the specificity of cell cycle specificity , Which inducedcell death in G_1 phase, and blocked G_2/M phase.HCPT also showed a remarkable cell cyclespecificity,by inducing cell death and apoptosis inG_1 phase and arrest of proliferation at S phase.CONCLUSION As_2O_3 and HCPT exhibitsignificant cytotoxicity on gastric cancer cells byinduction Of apoptosis.As_ 2O_3 and HCPT might have a pleasant prospect in the treatment ofgastric cancer,which needs to be further studied.
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