Midazolam Suppresses Hepatocellular Carcinoma Cell Metastasis and Enhances Apoptosis by Elevating miR-217

Abstract

Background. Hepatocellular carcinoma (HCC) is a significant cause of human death in the world. Recently, it is found that midazolam can modulate miRs to participate in HCC progression. This research project was designed to elucidate the impacts of midazolam and miR-217 on HCC cell metastasis and apoptosis. Methods. Human HCC cell strains (Hep3B and SK-HEP-1) were selected and intervened by midazolam at different concentrations in our research. miR-217-inhibitor intervened in the two HCC cell strains to observe the alterations of cell migration, invasiveness, and apoptosis. The miR-217 level in HCC cells was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results. As midazolam concentration was elevated, Hep3B and SK-HEP-1 viabilities were more obviously suppressed. The 10 μg/mL concentration was selected for analysis since Hep3B and SK-HEP-1 had an IC50 of 10.57 μg/mL and 9.35 μg/m, respectively. The qRT-PCR results showed the decreased of miR-217 in HCC cells, which was enhanced notably by midazolam intervention. Compared with the blank group, the invasiveness and migration (Transwell assay) of miR-217-inhibitor-transfected HCC cells were distinctly enhanced and the apoptosis rate (flow cytometry) was noticeably reduced. Conclusion. Midazolam can upregulate miR-217 in HCC cells, thus inhibiting HCC cell metastasis and apoptosis.

Role of midazolam on cancer progression/survival - An updated systematic review

“…In this review, midazolam inhibited cancer cell progression in various cancer cell lines; human non-small cell lung cancer (NSCLC)[ 18 , 19 , 22 , 23 ] and hepatocellular carcinoma[ 20 , 25 , 26 ] were the most studied cancer types. Midazolam also suppressed the progression of human T-cell lymphoma and neuroblastoma,[ 9 ] oral squamous cell carcinoma and glioblastoma,[ 10 ] hypopharyngeal squamous cell carcinoma,[ 11 , 13 ] leukaemia and colon cancer,[ 12 ] mouse Leydig tumour,[ 14 , 17 ] neuroglioma,[ 18 ] melanoma,[ 21 ] pancreatic ductal adenocarcinoma,[ 24 ] breast cancer (oestrogen positive),[ 23 ] and malignant glioma.…”

“…[ 16 ] Midazolam appeared to inhibit cancer cell proliferation in hypopharyngeal squamous cell carcinoma, leukaemia, colon cancer, neuroglioma, NSCLC, breast, pancreatic, glioblastoma, and hepatocellular carcinoma. Midazolam also exerted anti-metastatic properties by inhibiting cancer cell migration,[ 18 , 20 , 23 , 25 , 26 ] invasion,[ 18 , 20 , 23 , 26 ] and epithelial–mesenchymal transition. [ 23 ] Midazolam also decreased lung metastasis of melanoma cells by demonstrating an inhibitory effect on the vascular endothelial cells, with no direct effect on the migration or the proliferation of the melanoma cells.…”

Midazolam exhibits antitumour and enhances the efficiency of Anti-PD-1 immunotherapy in hepatocellular carcinoma

“…Zhang et al found that MDZ inhibited the proliferation and metastasis of hepatoma cells through the USP14/PI3K/Akt signalling pathway [ 18 ]. In addition to its sedative, hypnotic, and muscle relaxant effects, Shen et al found that MDZ also appears to exert inhibitory effects on hepatocellular carcinoma [ 19 ]. In this study, by constructing an HCC xenograft C57BL/6 mouse model, the anti-HCC effect of MDZ in vivo was also confirmed, and this effect was significantly increased when MDZ was combined with a PD1 monoclonal antibody.…”

Retracted: Midazolam Suppresses Hepatocellular Carcinoma Cell Metastasis and Enhances Apoptosis by Elevating miR-217

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”