Abstract
Aim Pancreatic cancer is one of the most quickly fatal cancers around the world. Burgeoning researches have begun to prove that mitochondria play a crucial role in cancer treatment. Mitofusin2 (Mfn2) plays an indispensable role in mitochondrial fusion and adjusting function. However, the role and underlying mechanisms of Mfn2 on cell autophagy of pancreatic cancer is still unclear. Our aim was to explore the effect of Mfn2 on multiple biological functions involving cell autophagy in pancreatic cancer. Methods Pancreatic cancer cell line, Aspc-1, was treated with Ad-Mfn2 overexpression. Western blotting, caspase-3 activity measurement, and CCK-8 and reactive oxygen species (ROS) assay were used to examine the effects of Mfn2 on pancreatic cancer autophagy, apoptosis, cell proliferation, oxidative stress, and PI3K/Akt/mTOR signaling. The expression of tissue Mfn2 was detected by immunohistochemical staining. Survival analysis of Mfn2 was evaluated by OncoLnc. Results Mfn2 improved the expression of LC3-II and Bax and downregulated the expression of P62 and Bcl-2 in pancreatic cancer cells. Meanwhile, Mfn2 also significantly inhibited the expression of p-PI3K, p-Akt, and p-mTOR proteins in pancreatic cancer cells. In addition, Mfn2 inhibited pancreatic cancer cell proliferation and ROS production. Assessment of Kaplan-Meier curves showed that Mfn2− pancreatic cancer has a worse prognosis than Mfn2+ pancreatic cancer has. Conclusions Our finding suggests that Mfn2 induces cell autophagy of pancreatic cancer through inhibiting the PI3K/Akt/mTOR signaling pathway. Meanwhile, Mfn2 also influences multiple biological functions of pancreatic cancer cells. Mfn2 may act as a therapeutic target in pancreatic cancer treatment.
Highlights
Accompanied with nearly 100% of 5-year mortality rate, pancreatic cancer is one of the most quickly fatal cancers around the world [1]
More and more evidence shows that tumor suppressors and key oncogenes modify the mitochondrial dynamics through significant signaling pathways and that function and mitochondrial mass variables in different tumors and individuals [6, 7]
Compared to the control group, proliferation of Aspc-1 cells was inhibited by Mfn2 overexpression (Figure 1)
Summary
Accompanied with nearly 100% of 5-year mortality rate, pancreatic cancer is one of the most quickly fatal cancers around the world [1]. In recent year we have some amazing improvements in the development of surgery, radiation therapy, and chemotherapy, pancreatic cancer still has a desperate prognosis, mainly because of its aggressive biological behavior and late breaking out of symptoms for clinical diagnosis [2]. Mitochondria play a significant role in the intermediates needed for macromolecule biosynthesis and the production of ATP [3]. Current evidence suggests that biosynthesis, signaling, and mitochondrial bioenergetics are needed for tumorigenesis [4]. Burgeoning researches have begun to prove that mitochondria play a crucial role in cancer treatment [5]. More and more evidence shows that tumor suppressors and key oncogenes modify the mitochondrial dynamics through significant signaling pathways and that function and mitochondrial mass variables in different tumors and individuals [6, 7]
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