Analgesic Anti-tumor Peptide Agap Human Glioma Cell Shg-44 Inhibition Of Proliferation And Migration

Malignant gliomas, the most common subtype of primary brain tumors, are characterized by high proliferation, great invasion, and neurological destruction and considered to be the deadliest of human cancers. Although various treatments for gliomas are developing, the expectancy of patients with malignant glioma is poor. In traditional Chinese medicine, the scorpion Buthus martensii Karsch has been one of the indispensable materials used in the treatment of many diseases since the Sung Dynasty. Scorpion toxin contains various toxic polypeptides with different functions. Analgesic-antitumor peptide (AGAP), one of scorpion toxic polypeptides, has been shown to have antitumor activity. In our study, the proliferation, cell cycle and migration of human malignant gliomas cells SHG-44 treated by rAGAP were analyzed by way of MMT assay, flow cytometry assay and Monolayer wound healing assay. These results showed that that recombinant AGAP (rAGAP) not only inhibits the proliferation of gliomas cell SHG-44 and rat glioma cell C6, but also suppresses the migration of SHG-44 cells during wound healing. To explain these phenomena, The mRNA and protein expression of SHG-44 cells treated by rAGAP were detected by means of western blot, RT-PCR and Gelatin zymography. We found that rAGAP leads to cell cycle of SHG-44 arrested in G1 phase accompanied by suppressing G1 cell cycle regulatory proteins CDK2, CDK6 and p-RB by means of the down-regulated protein expression of p-AKT. Meanwhile, rAGAP significantly decreases the activation of p-p38, p-c-Jun and p-Erk1/2, reduces the protein expression of NF-κB and BCL-2, and further suppresses the activation of VEGF and MMP-9 in SHG-44 cells. These findings suggest rAGAP inhibit proliferation and migration of SHG-44 cells by arresting cell cycle and interfering p-AKT, NF-κB, BCL-2 and MAPK signaling pathways.