Isocorydine inhibits the proliferation of human endometrial carcinoma HEC-1B cells by downregulating the Ras/MEK/ERK signaling pathway

نویسندگان

چکیده

Objective: Isocorydine (ICD), an aporphine alkaloid, plays a role in anticancer activity that is still being evaluated. However, the exact function and mechanism of ICD endometrial carcinoma largely unknown. Methods: MTT, flow cytometry, western blot, immunofluorescence, RT-PCR ELISA were used this research. Results: In our study we showed inhibited HEC-1B cell proliferation at certain times concentrations. Simultaneously, induced cells apoptosis. Further investigation indicated reduced phosphorylation protein levels c-Raf (rapidly accelerated fibrosarcoma), MEK1/2 (MAPK/Erk kinase) ERK1/2 (extracellular regulated kinase). Moreover, immunofluorescence assay confirmed intracellular expression Ras then promoted FOXO3 (forkhead box O3) nuclear localization to furtherly increase mRNA level Bim p27Kip1. Additionally, enzyme-linked immunosorbent (ELISA) revealed production EGF (epidermal growth factor) PDGF (Platelet-Derived Growth Factor), which indirectly activation Ras/MEK/ERK signaling pathway ligand level. Conclusion: Taken together, these data suggest for first time inhibits induces apoptosis through suppressing signaling, may provide theoretical foundation application treatment human carcinoma.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Regulation of the human leukaemia inhibitory factor (LIF) promoter in HEC-1B endometrial adenocarcinoma cells.

Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine which has been found to be expressed in the human endometrium and to play an important role in human reproduction. In the present study we investigated expression and regulation of the human LIF promoter in HEC-1B endometrial adenocarcinoma cells using a luciferase reporter plasmid bearing a 666 bp promoter fragment (h666LIF-Luc) in tr...

متن کامل

An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma

In our previous studies, we reported that CD133(+) cancer stem cells (CSCs) were chemoresistant in hepatocellular carcinoma (HCC) and that isocorydine treatment decreased the percentage of CD133(+) CSCs. Here, we found that a derivative of isocorydine (d-ICD) inhibited HCC cell growth, particularly among the CD133(+) subpopulation, and rendered HCC cells more sensitive to sorafenib treatment. d...

متن کامل

Metformin inhibits the migration and invasion of esophageal squamous cell carcinoma cells by downregulating the protein kinase B signaling pathway

Previous studies have suggested that metformin, a biguanide family member widely used as an oral antidiabetic drug, may inhibit proliferation and induce apoptosis in certain types of cancer cell. However, the molecular mechanisms underlying metformin-associated anticancer effects, and in particular antimetastatic effects, remain to be fully understood. The present study assessed the efficacy of...

متن کامل

In vitro cytotoxicity of 4'-OH-tamoxifen and estradiol in human endometrial adenocarcinoma cells HEC-1A and HEC-1B.

Tamoxifen (TAM), used to treat estrogen receptor (ER)-positive breast cancer, is a well known estrogen antagonist in the breast, but a partial estrogen agonist in the endometrium. In addition, TAM metabolites, such as 4'-hydroxy-tamoxifen (4-OH-TAM), have been shown to be more potent than the parent compound. The objective of this study was to determine the effects of 4-OH-TAM and estradiol (E2...

متن کامل

MicroRNA-34a inhibits cells proliferation and invasion by downregulating Notch1 in endometrial cancer

MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that regulate the expression of approximately 30% of human protein coding genes. Dysregulation of miRNAs plays a pivotal role in the initiation and progression of malignancies. Our study has shown that microRNA-34a (miR-34a) was upregulated in human endometrial cancer stem cells (ECSCs). However, it is unknown how miR-34...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: European Journal of Gynaecological Oncology

سال: 2021

ISSN: ['2709-0086', '0392-2936']

DOI: https://doi.org/10.31083/j.ejgo.2021.03.5225