Higher Expression Of Caveolin-1 Could Inhibit Human Small Lung Cancer Cells(SLCC) Apoptosis

Objective:Lung cancer has been recognized as the leading cause for cancer death in the world. SCLC, accounting for 20%-25%of all lung cancer cases is featured with the lowest differentiation, poorest prognosis and highest racurrence among all the lung cancers. And the surgical treatment for SCLC nearly has no significance. Now, the treatment for SCLC is mainly through chemotherapy combined with radiotherapy. And the treatment principles of radiotherapy and chemotherapy are both closely associated with apoptosis. More and more studies have found that Caveolin-1 plays an important role in the development of a variety of human cancers in different aspects. The previous research of ourown labratory had proved that Caveolin-1 could inhibit the proliferations of SCLC cells and increase the cell invasiveness at the same time. Although there are many evidences have proved that Caveolin-1 has an important regulatory role in apoptosis in many tomer cells, but the direct evidence for a relationship between Caveolin-1 and SCLC cell apoptosis have not be found. This study was performed to investigate the influences of the higher expression of Caveolin-1 on the apoptosis of SCLC cells in vitro.Methods:1.In our pervious study, the CAV-1 plasmid and the empty vector were stably transfected into the SCLC cell NCl-H446, and establish the stable cell lines--H446-neo and H446-Cav1. At first, the expression of Caveolin-1 in the cells NCl-H446, H446-neo and H446-Ca1 was examined by Western blot.2. CDDP and UVR (Ultraviolet radiation) were used to induce apoptosis, simulating chemotherapy and radiotherapy in clinic.3. Then we use a series of apoptosis methods, such as DAPI staining, TdT-mediated biotinylated-dUTP nick end labling (TUNEL), Flow cytometry analysis (FCM) to investigate the impact of higher expression of Caveolin-1 in Human Small Cell Lung Cancer (SCLC) NCI-H446 cell line, and H446-Cav-1 stable transfected cells, and the mock transfection of H446-neo by empty plasmid, on CDDP or UVR induced apoptosis.4. We use Western-blot assay to detect the expression change of apoptosis-associated protein, such as Caspase-3 and Bcl-2 in NCI-H446, H446-neo, and H446-Cav-1, after treated with CDDP or UVR.Results:1. We found that the expresson of Caveolin-1 in H446-Cav1 was higher than both NCI-H446 and H446-neo by Western Blot.2. After apoptosis methods, we find that:H446-CAV-1 cells had lower cell apoptosis rate compared with NCl-H446 and H446neo cells, and no difference was observed between NCl-H446 and H446-neo.3. By Western-blot assay, we also find that:compared with NCl-H446 and H446neo cells, the tendence of the change of Caveolin-1 expression in was reducing; and no difference was observed between NCl-H446 and H446-neo.Conclusion:Taken together, this investigation provided that higher expression of Caveolin-1 could inhibit SCLC apoptosis. And at the same time, we also found that higher expression of Caveolin-1 could decrease Caspase-3cleavages, and increase the stability of Bcl-2 on the molecular level.