MCL1 regulates cell death, tumor growth and chemosensitivity to sabutoclax in ovarian adenocarcinoma.

Abstract

This research was conducted to study the role of MCL1 in ovarian adenocarcinoma cell death and survival as well as chemosensitivity to sabutoclax. Both in vitro and in vivo assays including qRT-PCR, Western blot, CCK-8, caspase 3/7 activation, colony foci formation assay and xenograft assay were conducted. Except for the xenograft assay, the other experiments were conducted at the cellular level and they were carried out to assess cell activities such as viability, programmed death and proliferation. SKOV3 and OVCAR3 cell lines were used as the cell models for all experiments. It was proved that MCL1 was overexpressed in ovarian adenocarcinoma (tissues and cells) at RNA and protein levels. MCL1 knockdown was also discovered to suppress the viability and proliferation of ovarian adenocarcinoma cells in vivo and in vitro. Lastly, it was found that MCL1 knockdown significantly promoted ovarian carcinoma cell death and the sensitivity to sabutoclax. Thus, we concluded that MCL1 acted as a cancer facilitator in ovarian adenocarcinoma and it is also a suppressor of sabutoclax sensitivity.

• Authors: Cui Li, Yuchun Song, Pan Li
• Journal: Cell and tissue research (Cell Tissue Res) Vol. 379 Issue 3 Pg. 625-633 (Mar 2020) ISSN: 1432-0878 [Electronic] Germany
• PMID: 31754782 (Publication Type: Journal Article)

Chemical References

• 1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-N5-(2-phenylpropyl)-N5'-(2-phenylpropyl)-2,2'-binaphthyl-5,5'-dicarboxamide
• MCL1 protein, human
• Myeloid Cell Leukemia Sequence 1 Protein
• RNA, Messenger
• Gossypol

Topics

• Adenocarcinoma (drug therapy, genetics, metabolism, pathology)
• Animals
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm
• Female
• Gene Expression
• Gene Knockdown Techniques
• Gossypol (analogs & derivatives, pharmacology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Myeloid Cell Leukemia Sequence 1 Protein (biosynthesis, genetics)
• Ovarian Neoplasms (drug therapy, genetics, metabolism, pathology)
• RNA, Messenger (genetics, metabolism)
• Random Allocation
• Xenograft Model Antitumor Assays