The Experimental Studies Of Tumor Necrosis Factor Related Apotosis-Inducing Ligand(TRAIL) On Proliferation And Apoptosis Of Breast Cancer Cell Lines In Vitro

Breast cancer is the most common malignant tumor among woman and affects the health and life of woman seriously. HER-2/neu belongs to a member of the epidermal growth factor receptor superfamily and the expression of HER-2/neu is upregulated in 25%-30% patients with breast carcinoma, which is associated with poor prognosis. The proportion of disease free survival and long-term survival has been improved significantly due to the advances in diagnosis and treatment. Chemotherapy, radiotherapy and hormone therapy continue to be the major treatment in breast cancer. Multidrug resistance or relapse is a main cause of failure of treatment. Herceptin, a target antibody of HER-2, has showed antitumor effects in those have HER-2/neu overexpression, but the antitumor effects is limited when Herceptin was used alone. So the problem we have to face is how to improve the treatment effects and reduce the side effects.Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a member of tumor necrosis factor (TNF) superfamily and was discovered by Wiley. TNF superfamily members include TNF-α, TNF-β, CD95L,CD40L, TRAIL,TNF-α, TNF-β, CD95L, CD40L have ever received considerable press for their inducing apoptosis in tumor but the clinical use was limited because of their acute toxicity. In vitro studies had indicated that TRAIL can induce apoptosis in many tumor cells, but nontoxic to normal tissues. The animal experiment also showed that TRAIL could induce regression of tumor xenograft and nontoxic to host normal tissue. So TRAIL may be a new anti-tumor factor. Recently studies indicated that some chemotherapy agents can upregulation the sensitivity of TRAIL-induced apoptosis in many tumors. This sensitivity also can be improved by ionizing radiation combined with TRAIL. Base on those reasons, we payed much attention to TRAIL alone, or combine with other anticancer regents in proliferation and apoptosis of breast cancer, and its implication in clinical application.In our experiment we employed MTT assay to investigate the proliferation effect of TRAIL and TRAIL combined with radiotherapy or Herceptin on breast cancer cell lines MCF-7 and SKBR-3 (which overexpressed HER-2 gene). The apoptosis were detected by flow cytometry. RT-PCR was used to analysis the expression of apoptosis related gene. The results showed that breast caner cell lines MCF-7 and SKBR-3 were not sensitive to TRAIL, but the proportion of inhibition and apoptosis significantly improved when TRAIL was combined with irradiation in MCF-7 cell lines. RT-PCR indicated the expression of BCL-2 and BCL-XL gene were down regulated when MCF-7 cell lines were treated with irradiation combined with TRAIL. Combination of TRAIL with Herceptin also resulted in higher inhibitory and apoptosis rates than those either drug alone.TRAIL is a novel anticancer factor with the characteristics of inducing tumor apoptosis but nontoxic to normal tissues and may has a promising prospect in clinical use.