Abstract
Magnolol, a hydroxylated biphenyl extracted from Magnolia officinalis, has recently drawn attention due to its anticancer potential. The present study was aimed to explore the effects of Magnolol on restraining the proliferation, migration and invasion of pancreatic cancer in vivo and in vitro. Magnolol showed significant anti-growth effect in an orthotopic xenograft nude mouse model, and immunohistochemical staining of the xenografts revealed that Magnolol suppressed vimentin expression and facilitated E-cadherin expression. The cytoactive detection using CCK-8 assay showed Magnolol inhibited PANC-1 and AsPC-1 concentration-dependently. Scratch healing assay and the Transwell invasion assay proved the inhibiting effects of Magnolol on cellular migration and invasion at a non-cytotoxic concentration. Western blot and rt-PCR showed that Magnolol suppressed epithelial-mesenchymal-transition by increasing the expression level of E-cadherin and decreasing those of N-cadherin and vimentin. Magnolol suppressed the TGF-β/Smad pathway by negatively regulating phosphorylation of Smad2/3. Moreover, TGF-β1 impaired the antitumor effects of Magnolol in vivo. These results demonstrated that Magnolol can inhibit proliferation, migration and invasion in vivo and in vitro by suppressing the TGF-β signal pathway and EMT. Magnolol could be a hopeful therapeutic drug for pancreatic malignancy.
Highlights
Pancreatic cancer is a common malignancy and ranks as the 7th leading cancer-associated mortality in developed nations [1]
Accumulated evidence demonstrates that transforming growth factor-b (TGFb) signaling is a prime inducer of EMT in the tumor microenvironment [6]
Western blot showed that incubation of cancer cells with Magnolol and Transforming Growth Factor b1 (TGF-b1) simultaneously markedly decreased the levels of E-cadherin and phosphorylation of Smad2/3 compared with incubation with TGF-b1 alone (Figures 7C–F). These results demonstrated that Magnolol suppressed the aggressive behavior of these cells by inhibiting TGF-b1-induced EMT
Summary
Pancreatic cancer is a common malignancy and ranks as the 7th leading cancer-associated mortality in developed nations [1]. Great improvement has been reached in surgery, chemotherapeutics and radiotherapeutics, the prognosis is still poor due to the local invasion and metastasis upon diagnosis [2, 3]. No definite cure strategy can be provided to treat the patients with advanced stages or metastasis [2]. It is urgent to develop new and effective drugs to treat pancreatic cancer. Epithelial-mesenchymal-transition (EMT) is an important segment in cancer invasion, metastasis, proliferation and maintenance of stem cell characteristics [4]. When EMT occurs, Magnolol Suppresses Pancreatic Cancer Development tumor cells lose epithelial integrity and cell polarity and gain an invasive and motile phenotype [5]. The increased pretreatment of soluble TGF‐b1 in serum of unresectable pancreatic cancer patients indicates a poor prognosis for chemotherapy [7]
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