[Toxicity of arsenic trioxide to human lung adenocarcinoma cell line SPCA1 and its mechanism].
OBJECTIVE
Arsenic trioxide (As2O3) showed good curative effect on acute promyelocytic leukemia (APL) in clinic. Now, As2O3 was used in experimental research of treating solid tumors,such as gastric cancer,head and neck tumors, esophageal cancer, etc. This study was to research the toxicity effect of As2O3 on human lung adenocarcinoma cell line SPCA1, and its mechanism.


METHODS
MTT assay was used to observe inhibitory effect of As2O3 on proliferation of SPCA1 cells; cell cycle changes,apoptosis-associated proteins,Fas and Bcl-2,and intracellular calcium ions (IECa(2+)) content in SPCA1 cells treated with different doses of As2O3 were measured by flow cytometry.


RESULTS
As2O3 inhibited proliferation of SPCA1 cells dramatically with a dosage-effect correlation (r=0.973,P< 0.05),its 50% inhibitory concentration (IC(50)) was 8.56 micromol/L. As2O3 enhanced Fas protein expression,and intracellular Ca(2+) content (P< 0.05),but didn't influence Bcl-2 protein expression (P >0.05). The cell cycle arrested in G2/M phase in SPCA1 cells treated with As2O3.


CONCLUSIONS
As2O3 could inhibit the growth of SPCA1 cells in vitro, its mechanism is probably associated with the increased Fas expression and intracellular Ca(2+) content,and cell cycle arrest.
Wei
Ling
L
Basic Research Center, Shandong Provincial Tumor Hospital, Jinan, Shandong 250117, P.R. China. xiaoyalqf@sina.com
Wang
Xing-Wu
XW
Zuo
Wen-Shu
WS
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D000077237:Arsenic Trioxide; D002118:Calcium