[Primary research on arsenic trioxide inhibiting human breast cancer cells growth and its mechanisms].
OBJECTIVE
The study was to research the biological effect and mechanisms of arsenic trioxide (As2O3) on human breast cancer cell line MDA-MB-231.


METHODS
The cytotoxicity was observed by MTT assay. Apoptosis was detected with Annexin V-FITC + PI dual parameter. Cell cycle and positive rate of proliferation cell nuclear antigen (PCNA), apoptosis associated protein Fas and bcl-2 and intracellular calcium ions (IECa(2+)) levels were measured by flow cytometry.


RESULTS
As2O3 could inhibit the growth of MDA-MB-231 cells dramatically. There was obvious dosage-effect correlation (r = 0.99, P < 0.01), its half inhibitory concentration (IC(50)) was 6.65 micromol/L. Apoptosis was observed in MDA-MB-231 cells treated with As2O3. As2O3 could increase Fas expression and IECa(2+) levels and decrease PCNA expression in MDA-MB-231 cells (P < 0.01). Cell cycle was arrested in S + G(2)/M phase, but bcl-2 protein expression were not affected (P > 0.05).


CONCLUSIONS
As2O3 could inhibit the growth of MDA-MB-231 cells dramatically and induce apoptosis. We proposed that its mechanisms were probably associated with the improved Fas expression and IECa(2+) levels and decreased PCNA expression and cell cycle arrest.
Wei
Ling
L
Cancer Research Center, Shandong Tumor Hospital, Jinan 250117, China.
Wang
Xing-wu
XW
Zuo
Wen-shu
WS
Song
Xian-rang
XR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D019014:fas Receptor / Q000096:biosynthesis
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D018809:Proliferating Cell Nuclear Antigen; D019014:fas Receptor; D000077237:Arsenic Trioxide; D002118:Calcium