Effect of Zanthoxylum acanthopodium methanol extract on CDK4 expression to cervical cancer

Cervical cancer is a disease from the Human papillomavirus (HPV) through transmission, virus persistence, clone development until infecting the cells in the cervical. This study is to determine CDK4 expression in cervical cancer cells after being given Zanthoxylum acanthopodium methanol extract (ZAM) and the histological description of cervical cancer cells. This study consisted of 5 treatment groups. K-: control group, K+: rats model of cancer, P1: rats model of cancer with a dose of 100mg/BW of ZAM, P2: rats model of cancer with a dose of 200 mg/BW of ZAM, and P3: rats model of cancer with a dose of 400 mg/BW of ZAM. The cervical tissue was prepared on paraffin blocks and given Immunohistochemistry staining. Results showed that the expression of CDK4 are reduced in the ZAM treatment at doses of 200 and 400mg/KgBW (P<0.05) in cervical histology, but in doses of 100mg/kg BW, many brown marks are still visible on the cervical tissue. These proteins will bind, inhibit proteins, cell cycle development, modulate cell division, and signal transduction pathways of apoptotic signaling. The injection of benzopyrene and given ZAM in cervical tissue affect hematological values. ZAM affects and improves cervical histology after benzopyrene injection. The extract of andaliman can be developed into a cervical cancer drug candidate.

The Role of CDK4 in the Pathogenesis of Pancreatic Cancer

Pancreatic cancer (PC) continues to have the lowest overall survival and the lack of effective early diagnosis. Cyclin-dependent kinase 4 (CDK4) plays a fundamental role in the orderly progression of the cell cycle, binding to cyclin D to promote the progression through the G1/2 transition. The inhibition of CDK4/6 has therefore gained substantial interest in the hope of new and effective therapeutics in multiple cancers, such as advanced metastatic breast cancer. While the use of these agents is encouraging, their potential is yet to be fully explored. In this study we used the GLOBOCAN database to understand the most recent epidemiology of PC, Human Protein Atlas and KEGG to highlight the role, prevalence, and significance on patient survival of CDK4 in PC. We found that CDK4 cannot be used as prognostic in PC and no significant differences were observed between CDK4 expression and the patient’s clinical status, though larger studies, especially concerning CDK4 protein expressions, are required for a more thorough understanding. The use of CDK4/6 inhibitors in PC is still in clinical trials. However, due to only modest improvements observed in the use of single-agent therapies, efforts have focused on combinatorial approaches.

CDK4: A Novel Therapeutic Target for Extramammary Paget’s Disease

BackgroundThe outcome of extramammary Paget’s disease (EMPD) is poor when it progresses to metastasis because of the lack of effective systemic therapies. Recently, CDK4-targeted therapy has attracted attention as a potential therapeutic target for some cancers. The aim of this study was to analyze the impact of CDK4 expression on the survival of patients with EMPD.MethodsWe retrospectively reviewed 110 patients with EMPD. We conducted immunohistochemical analysis of CDK4 and cyclin D1 expression, and assessed the association between their expression and survival.ResultsMost EMPD lesions (108/110, 98.2%) were positive for CDK4 staining and there was a positive correlation between CDK4 expression and cyclin D1 expression (r = 0.54, p &lt; 0.001). Tumor thickness (p = 0.0003) and the presence of regional lymph node metastasis (p = 0.015) were significantly associated with high CDK4 expression. Regarding invasive EMPD, the multivariate analysis did not show the correlation between the expression of CDK4/cyclin D1 and survival outcomes (HR: 3.14, p = 0.14).ConclusionThe overexpression of CDK4 was identified as a major risk factor for disease progression. CDK4-targeted therapy could thus be a novel treatment option for unresectable EMPD.

Interaction Between lncRNA SEMA3B-AS1 and CDK4 Mediated by mir-545 Regulates the Proliferation of Triple-Negative Breast Cancer Cells

BackgroundAlthought lncRNA SEMA3B-AS1 was known to be involved in the development of many types of cancer, the role of SEMA3B-AS1 in triple-negative breast cancer (TNBC) remains unknown. This study was to investigate the role and underlying mechanism of SEMA3B-AS1 in TNBC.The mRNA expression of SEMA3B-AS1, miR-545 and CDK4 in TNBC tissues and non-cancer tissues of TNBC patients (n = 69) was detected by RT-qPCR. The protein expression of CDK4 was detected by Western blot. Cell proliferation were evaluated by CCK-8 assay.ResultsWe found that the expression of SEMA3B-AS1 was downregulated in TNBC tissues. The expression of SEMA3B-AS1 was positively correlated with the expression of miR-545 and inversely correlated with the expression of CDK4. Overexpression of SEMA3B-AS1 or miR-545 resulted in the downregulation of CDK4. Moreover, miR-545 inhibitor attenuated the effect of SEMA3B-AS1 overexpression on CDK4 expression. SEMA3B-AS1 overexpression also resulted in the upregulation of miR-545. Overexpression of SEMA3B-AS1 or miR-545 decreased the rate of TNBC cell proliferation, while overexpression of CDK4 increased the rate of TNBC cell proliferation. In addition, miR-545 inhibitor attenuated the effect of SEMA3B-AS1 overexpression on cell proliferation.Interaction between SEMA3B-AS1 and CDK4 mediated by miR-545 regulates the proliferation of TNBC cells.

MicroRNA-338-3p Inhibits Proliferation and Promotes Apoptosis of Multiple Myeloma Cells Through Targeting Cyclin-Dependent Kinase 4

MicroRNA-338-3p (miR-338-3p) has been reported to be a tumor suppressor in multiple cancer types. However, the biological role of miR-338-3p and its underlying mechanism in multiple myeloma (MM) remain unclear. In the present study, we investigated the biological role and potential of miR-338-3p in MM. We found that miR-338-3p was significantly decreased in newly diagnosed and relapsed MM tissues and cell lines. Overexpression of miR-338-3p in MM cells significantly inhibited proliferation and promoted apoptosis, caspase 3, and caspase 8 activity. Bioinformatics algorithm analysis predicted that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-338-3p, and this was experimentally verified by a dual-luciferase reporter assay. Furthermore, overexpression of miR-338-3p inhibited CDK4 expression on mRNA and protein levels. Of note, the restoration of CDK4 expression markedly abolished the effect of miR-338-3p overexpression on cell proliferation, apoptosis, caspase 3, and caspase 8 activities in MM cells. Taken together, the present study is the first to demonstrate that miR-338-3p functions as a tumor suppressor in MM through inhibiting CDK4. This finding implies that miR-338-3p is a potential therapeutic target for the treatment of MM.