Lobaplatin inhibits breast cancer progression, cell proliferation while induces cell apoptosis by downregulating MTDH expression

Abstract

ObjectiveLobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with poor prognosis of BCa patients. This study was designed to investigate the effect of lobaplatin on MCF-7 cell proliferation and its association with MTDH expression.Patients and methodsClinical treatment for BCa using lobaplatin, in combination with other general chemotherapy drugs, was administered to 32 BCa patients. The safety, effectiveness, and prognosis in lobaplatin-treated BCa patients were compared with those in controls (n=32). In vitro experiments were performed in MCF-7 cells to investigate the effect of lobaplatin on cell proliferation, apoptosis, and MTDH expression.ResultsWe found the intraoperative local chemotherapy using lobaplatin was safe and effective for BCa treatment, in comparison with the patients administered general chemotherapy drugs. Treatment of MCF-7 cell cultures with lobaplatin significantly reduced cell proliferation and increased cell apoptotic percentage. The expression of MTDH and Bcl-2 was inhibited by lobaplatin and that of Bax was increased by lobaplatin. Moreover, we observed the inhibition of MTDH by shRNA reduced cell proliferation and enhanced cell apoptosis.ConclusionLobaplatin was a safe and effective adjuvant chemotherapy for BCa. The effect of lobaplatin on inhibiting MCF-7 cell proliferation and inducing cell apoptosis might be, as least in part, mediated by suppressing the expression of oncogene MTDH.

FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies

“…SCD1 inhibition has been reported before to inactivate the AKT signaling, seen in higher rates of cell apoptosis in human lung adenocarcinoma ( 72 ). FBXW7 promotes apoptosis of BC cells through the ubiquitination and proteolysis of the oncoprotein metadherin (MTDH) ( 73 ), whose expression is related to various pathways, for example, the AKT signaling pathway ( 74 ). Furthermore, the inhibition of MTDH gives rise to apoptosis of cancer cells probably due to the downregulation of the AKT signaling ( 75 , 76 ).…”

Lobaplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: a 5-year follow-up of a randomized, open-label, phase II trial

“…The mechanism of lobaplatin’s anti-neoplastic effect may be attributed to JNK (c-Jun N-terminal) phosphorylation, ROS activation (reactive oxygen species), cell pyroptosis, and apoptosis. 32 , 33 However, the specific mechanism by which lobaplatin facilitates TNBC elimination warrants further investigation.…”

MicroRNA-497-5p Functions as a Modulator of Apoptosis by Regulating Metadherin in Ovarian Cancer

“…It has been reported that efficient and tumor-specific knockdown of the MTDH gene attenuates paclitaxel resistance of breast cancer cells both in vivo and in vitro 9 . Down-regulation of MTDH expression can inhibit breast cancer progression and cell proliferation, and induce cell apoptosis in breast cancer 28 . Silencing the expression of MTDH increases the radiation sensitivity of SKOV3 OC cells and reduces their proliferation and metastasis 10 .…”