Abstract
Arsenic trioxide (ATO) has been found to exert its anti-cancer activity in various human malignancies. In our previous report, we have shown that ATO inhibited cell growth and invasion via downregulation of Skp2 in pancreatic cancer (PC) cells. It has been extensively demonstrated that microRNAs (miRNAs) play a pivotal role in tumorigenesis. ATO might induce PC cell apoptosis and regulate Skp2 downregulation through the regulation of miRNAs. One study has demonstrated that miR-330-5p exerts a tumor-suppressive function in PC cell lines. Here, we investigated the role of miRNA-330-5p in ATO-mediated anti-tumor activity and explored whether ATO could regulate miR-330-5p in PC cells. We found that ATO treatment upregulated the expression of miR-330-5p. Moreover, miR-330-5p inhibitor rescued the ATO-mediated tumor-suppressive function. The combination of miR-330-5p mimic with ATO reduced cell growth, motility, and invasion, and enhanced apoptosis to a greater degree in PC cells. This study suggests that the combination of miR-330-5p mimic with ATO may be a potential therapeutic strategy for the treatment of PC.
Highlights
Pancreatic cancer (PC) is one of the lethal malignant tumors with high morbidity and mortality
Arsenic trioxide (ATO) Upregulates miR-330-5p Expression in PC Cells To verify whether ATO could regulate miR-330-5p expression in PC cells, we treated the cells with 3 mmol/L ATO in Patu8988 and Panc-1 cells
ATO and miR-330-5p Govern the Viability of PC Cells We have previously reported that 3 mmol/L ATO inhibited cell growth in Patu8988 and Panc-1 cells.[10]
Summary
Pancreatic cancer (PC) is one of the lethal malignant tumors with high morbidity and mortality. In the United States, approximately 55,440 new cases of PC and 44,330 deaths were expected in 2018.1 The morbidity and mortality of PC in China have gradually increased in recent years.[2] Current therapies for PC are involved in surgery and chemotherapy. For most advanced PC patients, who missed the surgery time, chemotherapy is the preferred approach to offer symptomatic relief and extend the median survival modestly. The standard chemotherapy was gemcitabine alone or in combination with other chemotherapeutic agents;[3] the efficacy is still limited.
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