Abstract

Objective: To investigate the effects of sulfured polysaccharide from Undaria pinnatifida (SPUP) on the biological behaviors of ovarian cancer (OC) cells and its potential mechanism.Methods: Sulfated polysaccharide from Undaria pinnatifida (SPUP) was extracted and characterized through a combination of chemical analysis, IR spectra, UV-Vis, gas chromatography, and high-performance gel permeation chromatography. OC and human ovarian surface epithelial cells were used as working model in vitro for evaluation of SPUP’s therapeutic effects. A combination of CCK-8, Transwell, and flow cytometry assay was used to measure the proliferation, migration, invasion, and apoptosis of OC cells, respectively. In addition, the protein expression levels of cells were also measured by Western blot.Results: SPUP suppressed OC development from three different perspectives: 1) SPUP treatment significantly inhibited the proliferation of OC in a dosage-dependent manner (p < 0.05); 2) SPUP inhibited the migration and invasion of OC cells confirmed by scratch and Transwell experiments (p < 0.05); 3) SPUP induced apoptosis in OC cells and thus further inhibited the growth of OC cells evaluated using flow cytometry (p < 0.05). The underlying mechanism of the suppressing effects of SPUP might be related to the inhibition of the hedgehog (Hh) signaling pathway in OC cells after SPUP treatment. With additional suppression of the Hh signaling pathway, the anticancer effects of SPUP were enhanced (p < 0.05).Conclusion: Taken together, SPUP could inhibit the proliferation, migration, and invasion and induce apoptosis of OC cells by inhibiting the activation of the Hh signaling pathway, which proposes SPUP as a novel drug to treat OC clinically.

Highlights

  • There are approximately 239,000 new cases of ovarian cancer (OC), the deadliest gynecological tumor in women, developed and 152,000 deaths worldwide every year (Ferlay et al, 2015)

  • This study aimed to study the effects of Sulfated polysaccharide from Undaria pinnatifida (SPUP) on cell proliferation, migration, invasion, and apoptosis in OC epithelial cells and further investigate its potential mechanism, providing novel insights for further potential identification of SPUP as a therapeutic drug in OC treatment

  • This study found that SPUP could inhibit the proliferation, migration, and invasion of OC cells and induce apoptosis

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Summary

Introduction

There are approximately 239,000 new cases of ovarian cancer (OC), the deadliest gynecological tumor in women, developed and 152,000 deaths worldwide every year (Ferlay et al, 2015). Due to the difficulty of early diagnosis and the drug resistance of chemotherapy, OC has become the leading cause of death in patients with gynecological malignant tumors (Torre et al, 2018), among which epithelial OC is the most critical pathological subtype of OC, accounting for 90% of primary ovarian malignant tumors (Mutch and Prat, 2014; Fu et al, 2016). Cytoreductive surgery combined with platinum and paclitaxel-based chemotherapy is the standard treatment strategy for epithelial OC. About 70% of patients relapse after the initial treatment and often develop resistance to platinum chemotherapy after recurrence (Chien et al, 2013). It is urgent to develop a new, safe, and effective drug with minor side effects to control the progression of OC and reduce patient mortality

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