Effects of propofol on colon cancer metastasis through STAT3/HOTAIR axis by activating WIF‐1 and suppressing Wnt pathway

Abstract

Background In the present study, we aim to investigate the potential role of propofol in the tumor progression of colon cancer. Methods Human colon cancer cell lines were cultured and exposed with 8 μg/mL propofol. RNA interference was performed to silence the expression of HOTAIR or STAT3 to explore their biological functions in colon cancer. Cell apoptosis and invasion were assessed using flow cytometry and transwell assays, respectively. Quantitative real‐time PCR, western blot, and immunohistochemistry were subjected to measure the expression patterns of HOTAIR, STAT3, Wnt signaling factors, and epithelial‐mesenchymal transition‐related markers, respectively. Besides, nude mice were transplanted with colon cancer cells for further exploration. Tumor formation, volume, and weight were evaluated to validate the in vitro findings. Results Propofol treatment promoted cell apoptosis and inhibited cell invasion in colon cancer cells, while the effects were reversed by HOTAIR overexpression. Additionally, STAT3 positively regulated HOTAIR expression, which was also negatively modulated by propofol. Moreover, STAT3 and HOTAIR were shown to independently regulate colon cancer cell apoptosis and invasion. Furthermore, HOTAIR could stimulate Wnt signaling pathway via inhibiting WIF‐1 expression and upregulating β‐catenin expression, which was also demonstrated by in vivo study. Conclusion Taken together, the current study demonstrated that propofol exerts the inhibition on cell invasion and promotion on cell apoptosis through regulating STAT3/HOTAIR by activating WIF‐1 and suppressing Wnt pathway, indicating that propofol might serve as a therapeutic role for colon cancer patients in the future.

RETRACTED ARTICLE: Propofol inhibits migration and induces apoptosis of pancreatic cancer PANC-1 cells through miR-34a-mediated E-cadherin and LOC285194 signals

“…Apart from its anesthetic effects, propofol also exerts a number of non-anesthetic effects, such as reduction of oxidative damage [37], decreases proinflammatory cytokines [38], inhibits COX-2 and PGE 2 functions and decrease surgery-induced neuroendocrine responses and cause less immunosuppression and recurrence of certain types of cancer [39,40]. In vitro and in vivo, propofol could inhibit invasion, migration, metastasis and induced apoptosis and cell cycle arrest of numerous cancer cells [12][13][14][15][16][17][18].…”

“…For example, propofol could inhibit in vitro cell growth and invasion by upregulating miR-140-5p in gastric cancer cells [12]. In human colon cancer cells in vitro and in vivo, propofol exerts its anti-tumor effect by activating WIF-1 and suppressing Wnt pathway [13]. In lung cancer A549 cells in vitro, propofol inhibited cell growth, migration and invasion by regulating miR-372/Wnt/β-catenin pathways [14].…”

Propofol Inhibits the Progression of Cervical Cancer by Regulating HOTAIR/miR-129-5p/RPL14 Axis

“…Zhang et al claimed that propofol could retard colon cancer progression by regulation of STAT3/HOTAIR axis through activating WIF-1 and repressing Wnt pathway. 24 Moreover, propofol was identified to inhibit tumor size and cell viability and facilitate apoptosis in CC by decreasing HOTAIR and mTOR pathway. 14 Our results presented that HOTAIR level was evidently declined in CC cells following propofol treatment in a dose-dependent way.…”

<p>Anesthesia Options and the Recurrence of Cancer: What We Know so Far?</p>

“…Most in vitro and in vivo animal studies indicate that propofol has significant anti-metastatic effects. 113,114 One of the proposed mechanisms is the downregulation of the STAT3/HOTAIR signaling pathway, which suppresses transcription factors Slug and HIF-1α and induces silencing of the NET1 gene; all changes associated with decreased migration and invasion in cancer cells. A second mechanism involves the upregulation of miR-124-3p.1, miR-135b, miR-361, miR-410-3p, miR-328, and lncRNA DGCR5.…”