Cooperative Treatment of Gastric Cancer Using B7-H7 siRNA and Docetaxel; How Could They Modify Their Effectiveness?

Purpose: Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemosensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with docetaxel on GC cells. Methods: MTT test was applied to determine the IC50 of docetaxel and the combined effect of B7-H7 siRNA and docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony-forming ability, wound healing assay and colony formation test were employed, respectively. Results: B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and docetaxel in MKN-45 GC cells. Also, B7-H7 suppression alongside docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes. Conclusion: B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with docetaxel, may be a promising therapeutic approach in treating GC.

miR-200c increases the sensitivity of breast cancer cells to Doxorubicin through downregulating MDR1 gene.

BACKGROUND: Breast cancer (BC) has been known as the most common type of cancer worldwide and resulted in death among women. BC is usually resistant to standard therapies that are significant problems in managing BC patients. miR-200c belongs to the miRNA family, which is considered as a tumor suppressor with reduced expression levels in various kinds of cancer like BC. Increased expression of miR-200c has been reported as a potent inhibitor of drug resistance and tumor advancement. The purpose of this paper is to examine the outcome of miR-200c restoring on enhancing the BC cells' sensitivity to Doxorubicin through downregulating the MDR1 expression. METHODS: Initially, MDA-MB-231 cells were transfected with miR-200c to perform functional analyses. After that, MTT assay was performed to investigate the viability of the cell. Finally, qRT-PCR was used to assess gene expression. RESULTS: According to the results, the miR-200c expression was downregulated in BC cells compared to control. Moreover, the cell viability was reduced in transfected cells via regulation in gene expression associated with apoptosis. Furthermore, miR-200c could increase the BC cells' sensitivity to Doxorubicin by reducing the MDR1 gene expression. CONCLUSION: Hence, this study's findings recommend that miR-200c can consider as a method of therapy for the treatment of BC.

The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment.

Gastric cancer (GC), with a heterogeneous nature, is the third leading cause of death worldwide. Over the past few decades, stable reductions in the incidence of GC have been observed. However, due to the poor response to common treatments and late diagnosis, this cancer is still considered one of the lethal cancers. Emerging methods such as immunotherapy with immune checkpoint inhibitors (ICIs) have transformed the landscape of treatment for GC patients. There are presently eleven known members of the B7 family as immune checkpoint molecules: B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), B7-DC (PDCD1LG2, PD-L2, CD273), B7-H2 (B7RP1, ICOS-L, CD275), B7-H3 (CD276), B7-H4 (B7x, B7S1, Vtcn1), B7-H5 (VISTA, Gi24, DD1α, Dies1 SISP1), B7-H6 (NCR3LG1), B7-H7 (HHLA2), and Ig-like domain-containing receptor 2 (ILDR2). Interaction of the B7 family of immune-regulatory ligands with the corresponding receptors resulted in the induction and inhibition of T cell responses by sending co-stimulatory and co-inhibitory signals, respectively. Manipulation of the signals provided by the B7 family has significant potential in the management of GC.

Nicotinic acetylcholine receptors in chemotherapeutic drugs resistance: An emerging targeting candidate.

There is no definitive cure for cancer, and most of the current chemotherapy drugs have limited effects due to the development of drug resistance and toxicity at high doses. Therefore, there is an ongoing need for identifying the causes of chemotherapeutic resistance, and it will be possible to develop innovative treatment approaches based on these novel targeting candidates. Cigarette smoking is known to be one of the main causes of resistance to chemotherapeutic agents. Nicotine as a component of cigarette smoke is an exogenous activator of nicotinic acetylcholine receptors (nAChRs). It can inhibit apoptosis, increase cell proliferation and cell survival, reducing the cytotoxic effects of chemotherapy drugs and cause a reduced therapeutic response. Recent studies have demonstrated that nAChRs and their downstream signaling pathways have considerable implications in different cancer's initiation, progression, and chemoresistance. In some previous studies, nAChRs have been targeted to obtain better efficacies for chemotherapeutics. Besides, nAChRs-based therapies have been used in combination with chemotherapy drugs to reduce the side effects. This strategy requires lower doses of chemotherapy drugs compared to the conditions that must be used alone. Here, we discussed the experimental and clinical studies that show the nAChRs involvement in response to chemotherapy agents. Also, controversies relating to the effects of nAChR on chemotherapy-induced apoptosis are in our focus in this review article. Delineating the complex influences of nAChRs would be of great interest in establishing new effective chemotherapy regimens.

Molecular pathways in the development of HPV-induced cervical cancer.

Recently, human papillomavirus (HPV) has gained considerable attention in cervical cancer research studies. It is one of the most important sexually transmitted diseases that can affect 160 to 289 out of 10000 persons every year. Due to the infectious nature of this virus, HPV can be considered a serious threat. The knowledge of viral structure, especially for viral oncoproteins like E6, E7, and their role in causing cancer is very important. This virus has different paths (PI3K/Akt, Wnt/ß-catenin, ERK/MAPK, and JAK/STAT) that are involved in the transmission of signaling paths through active molecules like MEK (pMEK), ERK (pERK), and Akt (pAkt). It's eventually through these paths that cancer is developed. Precise knowledge of these paths and their signals give us the prognosis to adopt appropriate goals for prevention and control of these series of cancer.