scholarly journals Metformin Treatment Exerts Antiinvasive and Antimetastatic Effects in Human Endometrial Carcinoma Cells

2011 ◽  
Vol 96 (3) ◽  
pp. 808-816 ◽  
Author(s):  
Bee K. Tan ◽  
Raghu Adya ◽  
Jing Chen ◽  
Hendrik Lehnert ◽  
Louis J. Sant Cassia ◽  
...  

Context: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women associated with an increased risk of endometrial hyperplasia. We sought to study the effects of metformin treatment (widely used in the management of PCOS women) on human endometrial adenocarcinoma cells. Objectives: To study the effects of metformin treatment on in vitro invasion and metastasis in human endometrial adenocarcinoma cells. Also, given the link between inflammation with endometrial cancer invasion and metastasis, we explored the roles of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) as well as v-akt murine thymoma viral oncogene homolog 1 (Akt) and extracellular signal-regulated kinases (Erk1/2) signaling pathways. Design: Sera were obtained from PCOS and control subjects. In vitro invasion were assessed in human endometrial cells (ECC-1 cells) by wound-healing motility and migration assays. NF-κB was studied by stably transfecting ECC-1 cells with a cis-reporter plasmid containing luciferase reporter gene linked to five repeats of NF-κB binding sites. The gelatinolytic activities of secreted MMP-2/9 in conditioned media were measured by gelatin zymography. Akt and Erk1/2 phosphorylation were assessed by Western blotting. Results: In vitro invasion in ECC-1 cells was significantly attenuated by sera from PCOS women after 6 months of metformin treatment (850 mg twice daily) compared to matched controls (P < 0.01). These effects appear to be associated with NF-κB, MMP-2/9, as well as Akt and Erk1/2 pathways that are known to be important regulators of inflammation, tumor invasion and metastasis. Conclusions: Metformin, potentially, may serve as adjuvant treatment in the management of patients with endometrial cancer.

2009 ◽  
Vol 19 (1) ◽  
pp. 147-151 ◽  
Author(s):  
Aera R. Han ◽  
Yong-Soon Kwon ◽  
D. Y. Kim ◽  
J. H. Kim ◽  
Y. M. Kim ◽  
...  

Objectives:To evaluate the outcomes of pregnancy in young women (<40 years old) with early endometrial cancer or atypical complex hyperplasia who were treated by conservative management followed by assisted reproductive technology (ART).Materials and Methods:Medical charts of 11 patients treated from January 1997 to October 2007 at Asan Medical Center were retrospectively reviewed. These patients had all been treated with progestin and serial dilatation and curettage as primary fertility-preserving therapies.Results:After pathological remission of disease, 10 patients tried to become pregnant by ART, 4 by in vitro fertilization and embryo transfer, and 6 by controlled ovarian hyperstimulation, with or without intrauterine insemination. Eight women had intrauterine pregnancies, and 6 patients had live births. Patients have been followed up for 9 to 51 months (mean, 21 months) after delivery, with no evidence of tumor recurrence.Conclusions:Fertility-preserving therapy followed by ART can be a good option in well-selected patients with early endometrial cancer who want to become pregnant.


2020 ◽  
Author(s):  
Chunying Luo ◽  
Min Liu ◽  
Jianwei Zhang ◽  
Guoqiang Su ◽  
Zhonghua Wei

Abstract Background: Many studies have shown that microRNAs play key functions in nasopharyngeal carcinoma proliferation, invasion and metastasis. However, whether the dysregulated level of miRNAs contributes to the metabolic shift in nasopharyngeal carcinoma is not completely understood.Objectives: This study was conducted to explore the expression and function of miR-206 in nasopharyngeal carcinoma.Methods: miR-206 expression level was examined by real-time PCR. miR-206 inhibitor, mimics, and scrambled control were transiently transfected into nasopharyngeal carcinoma cells and their effects on colony formation, glucose uptake, and lactate secretion were observed in vitro. Moreover, the relationship between the levels of miR-206 and HK2 was examined by luciferase reporter and assay western blot.Results: In our study, we reported downregulation of miR-206 expression leads to metabolic change in nasopharyngeal carcinoma cells. miR-206 controls this function by enhancing HK2 expression. The enhancement of aerobic metabolism activity induced by miR-206 leads to the rapid proliferation of nasopharyngeal carcinoma cells.Conclusions: Our data demonstrated that miR-206 was involved in the regulation of Warburg effect in nasopharyngeal carcinoma by suppressing HK2 expression.


Author(s):  
Allakhyarov D.Z. ◽  
Petrov Yu.A. ◽  
Palieva N.V.

This article presents reviews of literature sources on the issue of assessing the risk of developing gynecological cancer in women after an in vitro fertilization program. Infertility and infertile marriages have now become quite a big problem of modern medicine. Against the background of the unfavorable demographic situation in the Russian Federation, this problem is becoming quite urgent. The main way to solve this situation is assisted reproductive technologies, among which the most common is in vitro fertilization. The in vitro fertilization program is accompanied by a hormonal ovulation stimulation procedure to obtain a female germ cell capable of fertilization. Against the background of the active use of the in vitro fertilization procedure, many patients had concerns related to the risk of developing gynecological cancer after the IVF procedure, which is due to the use of hormonal drugs to stimulate the ovaries. Also of concern is the fact that certain types of cancer, including ovarian cancer, endometrial cancer and breast cancer, are hormone-dependent. In this regard, multiple large-scale studies were conducted, which showed that the risk of developing gynecological cancer is really increased in patients after the in vitro fertilization program. In particular, breast cancer in women after the in vitro fertilization program is more common by 10%, and in women without a history of pregnancy and over the age of 40, it is more common by 31%. The increased risk may be due to age-related vulnerability to the effects of hormones or higher doses of hormones during the IVF procedure. Ovarian cancer and endometrial cancer are also more common in patients after IVF. According to the research results, it is suggested that it is not the IVF procedure itself that causes the development of cancer, but excessive hormonal load of the body, which leads to the launch of carcinogenesis.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
Nadire Kucukoztas ◽  
Selim Yalcin ◽  
Samed Rahatli ◽  
Ozlem Ozen ◽  
Nihan Haberal ◽  
...  

e15573 Background: Stage IC patients are at an increased risk of recurrence and overall worse prognosis compared with stage IA and IB patients. Adjuvant chemoherapy is utilized based on specific pathologic factors. The objective of this study is to evaluate treatment outcomes at a single institution in patients with 1988 FIGO stage IC endometrial adenocarcinoma. Methods: Records of the patients with FIGO stage IB (formerly IC) endometrial cancer were retrospectively evaluated. All patients were initially treated surgically with comprehensive staging lymphadenectomy. Results: A total of 85 patients were included. Patient and tumor characteristics are shown in the table. Median age of the patients was 60 (range 27-95). Fifty-nine patients had at least one co-morbid disease. Complete surgical staging including pelvic and paraaortic lymph node dissection was performed in all the patients. Sixteen patients (19%) received adjuvant chemotherapy, including 6 patients with serous cancer and one patient with small cell cancer. Paclitaxel/carboplatin was the preferred regimen in Median follow up was 30 months (range 10-61 months). Seven patients (8%) relapsed and 4 patients (5%) died on follow up. 5 year disease free survival was 89% and overall survival was 95%. One of the 16 patients (6.2%) who received chemotherapy and 6 of the 69 patients (8.7%) who did not receive relapsed/died on follow up. Survival analysis was not performed because of the low number of events in both groups. Conclusions: We found similar rates of recurrence and death with previous studies in stage IC endometrial cancer. Complete surgical staging is the mainstay of treatment. Marginally lower recurrence rate in chemotherapy treated patients delineate the need for prospective randomized data addressing the role of adjuvant systemic therapy in early-stage patients with endometrial adenocarcinoma. [Table: see text]


2009 ◽  
Vol 42 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Zhong-Lian Li ◽  
Syoko Morishima ◽  
Jin-Tian Tang ◽  
Yoshinori Otsuki

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Xinchao Deng ◽  
Congzhe Hou ◽  
Zhen Liang ◽  
Huali Wang ◽  
Lin Zhu ◽  
...  

Background. MicroRNA-202 (miR-202) has been reported to be aberrantly regulated in several cancers. The aim of this study is to explore the functional role of miR-202 in EAC tumor growth. Material and Methods. miR-202 expression was detected by qRT-PCR. TargetScan and luciferase reporter assay were used to elucidate the candidate target gene of miR-202. The FOXR2 protein level was assessed by Western blot and immunohistochemistry. Survival analysis was explored for FOXR2 expression in EAC patients. Results. miR-202 expression was significantly decreased in EAC tissues (P<0.01) compared with that in control tissues. And the downregulate miR-202 was significantly associated with poor prognosis (P<0.01). Re-expression of miR-202 dramatically suppressed cell proliferation in vitro and tumor growth in vivo. FOXR2 was identified as a direct target of miR-202. In EAC tissues, FOXR2 was upregulated and the increased FOXR2 was significantly associated with poor prognosis. In miR-202-transfected cells, the FOXR2 expression was inversely changed. The analysis of FOXR2 protein expression and miR-202 transcription in EAC tissues showed negative correlation (R=−0.429). Conclusion. miR-202 may function as a tumor suppressor in EAC tumor growth by targeting FOXR2 oncogene, which may provide new insights into the molecular mechanism and new targets for treatment of EAC.


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