Gossypol acetate induced apoptosis of pituitary tumor cells by targeting the BCL-2 via the upregulated microRNA miR-15a.

It is reported that gossypol acetate (GAA) has obvious effects on inhibiting the growth of tumors, by inhibiting the activity of enzymes. Ultrastructural study showed that GAA can cause morphological changes of mitochondria which leads to the apoptosis of tumors. However, little is known about the pathways that how the GAA triggers apoptosis of tumors and what kind of the molecular events have happened when GAA is added. The aim of the study is try to know if GAA have some functions on pituitary tumor cell. And if there are any changes after GAA treatment, we try to understand the mechanisms that how GAA regulate the growth of pituitary tumor cell. The study was carried out on rat lactotroph cell lines, GH3 and MMQ. Q-PCR and western blot (WB) assay are used to determine the expression level of genes and the protein level. Both the miR-15a (mimics) overexpression cell line and miR-15a knock out (inhibitor) cell line were obtained in GH3 and MMQ. Apoptosis rate was determined by flow cytometry (FCM). Our study revealed that: 1) GAA inhibits the proliferation of pituitary tumor cells of GH3, MMQ. 2) GAA upregulate the expression of miR15a in GH3 and MMQ. 3) Overexpressed miR-15a (mimics) downregulates the expression level of Bcl-2. 4) Knock down miR-15a (inhibitor) upregulates Bcl-2 and reverse the apoptosis induced by GAA. Our study indicates that GAA-induced decrease in cell proliferation is associated with decreased expression of Bcl-2 and increased miR-15a. Based on this, we propose developing GAA as a novel therapeutic tool in the management of pituitary tumor.