Forced Vasohibin-1 Expression Increases Paclitaxel Sensitivity of Ovarian Cancer by Inhibiting Microtubule Activity

Overview

Journal Cancer Rep (Hoboken)

Specialty Oncology

Date 2024 Dec 22

PMID 39710372

Authors

Takahiro Koyanagi

Yasushi Saga

Yoshifumi Takahashi

Kohei Tamura

Suzuyo Takahashi

Akiyo Taneichi

Yuji Takei

Hiroaki Mizukami

Hiroyuki Fujiwara

Affiliations

Soon will be listed here.

Abstract

Background: Vasohibin-1 (VASH1), an angiogenic inhibitor, exhibits tubulin carboxypeptidase activity, which is involved in microtubule functions. Paclitaxel, the core chemotherapeutic agent for ovarian cancer chemotherapy, has a point of action on microtubules and may interact with VASH1.

Aims: To examine the influence of VASH1 on intracellular tubulin detyrosination status, cyclin B1 expression, and paclitaxel chemosensitivity using VASH1-overexpressing ovarian cancer cell lines.

Methods And Results: Gene-transfected human ovarian cancer cell lines were subjected to western blot analysis. Western blot analysis of VASH1-overexpressing ovarian cancer cells revealed upregulated expression of detyrosinated tubulin and cyclin B1 compared with control cells. By WST-1 assay, paclitaxel chemosensitivity of VASH1-overexpressing ovarian cancer cells was markedly enhanced compared with that of control cells, whereas there was no significant difference in chemosensitivity to cisplatin. The forced expression of VASH1 enhanced tubulin carboxypeptidase activity and increased cyclin B1 expression, resulting in augmented paclitaxel chemosensitivity in ovarian cancer cells.

Conclusion: Ovarian cancer treatment strategies targeting VASH1 can potentiate the effects of conventional chemotherapy by inhibiting angiogenesis and regulating microtubule activity.

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