Anticancer drugs generally used to treat breast cancer are taxanes and platinum agents. Taxane drugs include things like paclitaxel and docetaxel for BRCA1 gene mutations or hormone-negative cancers. The positive-hormone cancers are significantly less sensitive to taxanes. Therefore, platinum agent anticancer drugs for instance cisplatin and doxorubicin are incorporated as an alternative to triple-negative breast cancer (lack of estrogen ERK8 manufacturer receptors, progesterone receptors, and ERBB2 receptors)[195]. Tight junctions (TJs) are structural proteins that handle transportation across the cell membrane. These proteins regulate cellular permeability although preserving cell polarity, restricting the diffusion of molecules by means of the membrane. Tight junctions also manage cellular functions, which includes cellular responses to environmental stimuli, intracellular gene expression, cell differentiation, and proliferation. TJs are composed of membrane proteins that can interact with adjacent cells, functioning as a barrier[200,201]. An integral component of TJs that offers structure and function is definitely the protein occludin, encoded by the occludin (OCLN) gene[202,203]. Occludin oxidizes NADH[204], which is important for TJ morphology, stability, barrier function, and localization on the plasma membrane on endothelial cells[200]. Occludin consists of a transmembrane domain with 4 membrane-spanning regions as well as other protein domains which include a C-terminus coiled-coil domain to interact with other proteins[200,203]. OCLN’s protein expression can influence the development of several cancer forms, such as ovarian cancer[200], lung adenocarcinoma[203,205], and breast cancer metastasis[206]. Zhang et al.[200] (2018) DOT1L MedChemExpress reported that OCLN overexpression improved transepithelial resistance, which indicates stronger TJs, though downregulation of OCLN resulted inside a decreased cell to cell adhesion phenotype (a widespread characteristic of tumors). A different study reported that OCLN overexpression stimulates malignant development of lung cancer cells, thereby promoting proliferation and blocking apoptosis[203]. Around the other side, eliminating the OCLN gene has been shown to promote tumorigenic factors and lower susceptibility to apoptosis in squamous cell carcinoma[201]. OCLN expression increases on A549 lung cancer cells market their resistance to cisplatin, doxorubicin, and gemcitabine. As an anticancer drug resistance mechanism, there is an improved expression of OCLN in the TJs of lung cancer cells. The overexpression of OCLN induces drug resistance by inhibiting the flux of doxorubicin, hence lowering drug concentration within the cell. OCLN may not be connected to cancer drug resistance acquisition directly, however it limits the chemosensitivity of anticancer drugs to lung cancer cells[205]. Within the A549 lung cancer cell line, OCLN knockdown was not connected straight to their resistance to anticancer drugs, but it suppressed their chemosensitivity on a multicellular spheroid assay. OCLN overexpression on A549 cells decreased doxorubicin permeability on account of their impact on signaling pathways, lowering the drug’s accumulation and cytotoxicity, major to anticancer drug resistance. Interestingly, spheroid cancer cells with an enhanced OCLN expression developed cisplatin resistance, showing the value of this gene in MDR[205].OccludinDRUG DELIVERY SYSTEMS Applying NANOPARTICLES To enhance THE EFFECTIVENESS OF CHEMOTHERAPEUTIC DRUGS IN RESISTANT TUMORSResearchers have adopted several techniques to incorporate carriers to de.
