Arsenic Trioxide Induces The Re-expression Of ER In Vitro

BackgroundBreast cancer is the most common cancer in women. The number of patients is more and more. Breast cancer is divided into two types by the difference of ER phaenotype:ER negative and ER positive. Endocrine therapy is often used in the clinical therapy of breast cancer patients(ER positive). But for negative patients, the effect is not obvious with endocrine treatment. If ER can re-express for ER-negative breast cancer patients, they will get a new ways of treatment. Estrogen receptor(ER) alpha gene expression silence' mechanism is not clear in ER alpha negative breast cancer.But study recently discovers that Estrogen receptor(ER)alpha gene expression silencing is probably associated with the CpG island methylation in the core Promoter of ER alpha gene and not due to generearrangement, mutation, absence. Arsenic trioxide which has been used to cure neoplastic hematologic disorder is a kind of traditional Chinese medicine with anti-tumor. In the treatment of solid tumors, it is speculated that gene ER may re-express by demethylation arsenic trioxide. With different concentrations of arsenic trioxide and tamoxifen for the tumor of mice (MDA-MB-435 cells were injected into nude mice), it can be observed the efficacy of solid tumors after treated by arsenic trioxide. The present study was designed to explored possibility and mechanism of re-expression of the silenced estrogen receptor gene in human breast cancer solid tumors by arsenic troxide(AS203).PurposeTo study the demethylation effect of arsenic trioxide (AS2O3) on ERa negative human breast cancer cells MDA-MB-435s and its possible mechanisms, and to observe the treatment efficacy of combined Tamoxifen (TAM) after the ERa re-expression.MethodMS-PCR was used to detect the methylation status of ERa gene after treated by AS2O3 in ERa negative human breast cancer solid tumors and the transplanted tumor tissue RT-PCR was used to detect the mRNA expression of ERa.ResultMS-PCR results showed that:ERa was demethylated after treated by AS2O3; RT-PCR results:ERa mRNA restored the expression after treated by AS2O3.ConclusionAS2O3 of definite Concentration could induce ERa gene re-expression in solid tumors (MDA-MB-435 cells were injected into nude mice) through DNA demethylation; As203 of definite Concentration could induce Era RNA gene re-expression in solid tumors (MDA-MB-435 cells were injected into nude mice); Arsenic trioxide can make ERa-negative expression restore positive expression and will open up new therapeutic approach for the breast cancer patients of ERa-negative.