Abstract
Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells’ proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent.
Highlights
Gastric cancer is the fourth fatal tumor around the world
When ANXA5 protein was applied to the murine melanoma xenograft model, tumor size and angiogenesis were remarkably reduced by suppressing VEGF expression [17], which implies that ANXA5 protein might be used as a kind of treatment agent; when ANXA5 was managed to form a complex with TRAIL, it can promote the TRAIL-induced apoptosis and increase cell sensibility to TRAIL [17, 18]
With the data preserved in the databases, we found that endogenous ANXA5 expression decreased significantly in the gastric cancer tissues when compared with the adjacent normal tissue
Summary
Gastric cancer is the fourth fatal tumor around the world. There are about 850 thousands new cases and 650 thousands death per year [1]. Accumulating researchers find that ANXA5 plays different roles in the development of various neoplasms such as ovary carcinoma [6], uterine cervical carcinoma [7], and colorectal carcinoma [8] where it is regarded as the diagnosis and prognosis marker It promotes cell proliferation and metastasis, suppressing cell apoptosis in cholangiocarcinoma [9], murine hepatocellular carcinoma [10], and glioblastoma multiforme [11]. When ANXA5 protein was applied to the murine melanoma xenograft model, tumor size and angiogenesis were remarkably reduced by suppressing VEGF expression [17], which implies that ANXA5 protein might be used as a kind of treatment agent; when ANXA5 was managed to form a complex with TRAIL, it can promote the TRAIL-induced apoptosis and increase cell sensibility to TRAIL [17, 18] All these imply that ANX5 has the potential to be used as a cancer therapy. Our data indicated that ANXA5 acts as oncogene suppressor in gastric cancer which might be through the MAPK/ERK pathway and has the potential to be an auxiliary treatment to gastric cancer
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