RESUMO
Nowadays, malignant tumor has become an important killer endangering human health, and the research on tumor has become a hot spot in the medical field. The CKLF-like MARVEL transmembrane domain containing family of genes (CMTM family), previously called chemokine-like factor super family (CKLFSF). CMTM family is a novel gene family firstly discovered by Chinese scholars and has a wide range of biological functions, which is closely related to human immune, hematopoietic and reproductive systems as well as tumors. CMTM family is dysregulated in many common tumors, can participate in a variety of signaling pathways closely related to the occurrence and development of cancer, which is closely related to the biological behavior changes of tumor cells. CMTM family members play an important role in the signaling molecular mechanisms that regulate the biological function of tumor cells and are able to regulate the signaling pathways of the tumor cell cycle and apoptosis. Including epithelial-mesenchymal transition process, epidermal growth factor receptor related signaling pathways, and closely related to the tumor immune microenvironment by regulating programmed death receptor-ligand 1. In this paper, we review the signaling molecular mechanisms of CMTM family in the biological processes of tumor cell proliferation, migration, invasion and apoptosis, as well as the potential clinical applications of CMTM family in ovarian cancer, breast cancer, liver cancer, gastric cancer, colorectal cancer, pancreatic cancer and other common malignant tumors. At present, the detailed molecular mechanism ofCMTM family related to tumor has not been fully clarified. Further study of the expression, biological role and regulatory mechanism of CMTM family in tumor will provide new ideas and targets for tumordiagnosis, treatment and prognosis prediction.
RESUMO
Lysophosphatidic acid (LPA), a bioactive lipid medium, plays an important role in the development and progression of ovarian cancer. Doxorubicin hydrochloride (DOX) is a first-line drug in the ovarian cancer clinical therapy, while the effect and molecular mechanism of LPA in the ovarian cancer with DOX treatment is still unclear. This study intended to explore the effect and molecular mechanism of LPA in ovarian cancer treated with DOX. SKOV3 and OVCAR-3 cells of human ovarian cancer and Chinese hamster ovary cells were treated with control, LPA (lOp-mol/L), DOX (2jjLmol/L) and LPA (10jJLmol/L) + DOX (2p,mol/L) respectively for 24 hours. The morphological changes of SKOV3 cells were observed under optical microscope and transmission electron microscope. Results showed that LPA reduced cell death and the degree of chromatin aggregation in SKOV3 cells treated with DOX; RT-qPCR showed that LPA treatment could down-regulate the mRNA levels of caspase-3 in DOX-treated SKOV3 cells (P<0. 05); Western blot showed that LPA treatment could reduce caspase-3 and cleaved caspase-3 levels treated with DOX in SKOV3, OVCAR-3 and CHO cells (P<0. 05); Flow cytometry using Annexin V/PI double staining showed that LPA could down-regulate apoptosis in SKOV3 cells treated with DOX (P<0. 05); DCFH-DA method was used to detect intracellular levels of reactive oxygen species (ROS) in SKOV3 cells. It was found that LPA reduced the intracellular ROS level treated with DOX (P<0. 05). Our preliminarily study showed the effect of LPA in the apoptosis of ovarian cancer treated with DOX, which may provide a reference for the drug therapy of ovarian cancer targeting LPA.