The Inhibition Effect of Caveolin-1 on PANC1 Human Pancreatic Tumor Growth In vitro and In vivo

Caveolin-1 is a transmembrane protein and essential structural constituent of the caveolae membrane. Caveolin-1 has been involved in multiple cellular functions and oncogenesis. To investigate the roles of caveolin-1, stable transfectants were established in PANC1 pancreatic adenocarcinoma cells which had up-regulated caveolin-1 expression. The plasmid pCI-neo-cav-1 and its corresponding empty vector (pCI-neo) were transfected into PANC1 cell lines. The expression of caveolin-1 in these three cell lines was determined by RT-PCR and Western blot. Cell cycle phase distribution was determined by flow cytometry. The colony formation ability of tumor cells was detected by anchorage-independent growth assay. Cell migration and invasion were assayed in MilliCell chambers. Xenograft tumor models in nude mice were developed. Immunohistochemistry was used to characterize Ki-67 levels in residual tumors, and apoptosis was evaluated by TUNEL technique. Caveolin-1 overexpression inhibited PANC1 cell proliferation by arresting the cell cycle in the G0/G1 phases and also markedly reduced the capacity of the cells to form colonies in soft agar. Additionally, caveolin-1 overexpression dramatically inhibited cells to invade and migrate. Importantly, in vivo experiments demonstrated that overexpression of caveolin-1 resulted in significant growth inhibition of the xenograft pancreatic tumors. Immunohistochemistry analysis demonstrated both a marked decrease in the number of proliferating tumor cells and an increase in the number of apoptotic tumor cells in PANC1/cav-1 xenograft tumors. The results provide an initial demonstration that caveolin-1 can function as a tumor suppressor rather than as a tumor promoter in PANC1 cells.