The Role and Mechanism of Human Papillomavirus16 E7 (HPV16 E7) in the Proliferation and Invasion of Cervical Cancer Cells Through Regulating Forkhead Box Protein A1

2020 ◽  
Vol 10 (8) ◽  
pp. 1206-1212
Author(s):  
Yunyan Ma ◽  
LV Xiaoyan ◽  
Xiaojiang Jia ◽  
Jingzhen Zhou ◽  
Zhenbo Ouyang ◽  
...  

High-risk HPV16 is an important factor for cervical cancer. HPV16 E7 can promote the malignant transformation of cervical epithelial cells. Forkhead box protein A1 (FOXA1) is abnormally expressed in several tumors. Our study assessed HPV16 E7's effect on cervical cancer cells. Hela cells were divided into control group; HPV16 E7 group; and siFOXA1+ HPV16 E7 group followed by analysis of HPV16 E7 and FOXA1 expression by Real-time PCR and Western blot, cell proliferation by MTT assay, Caspase 3 activity, Bax and Bcl-2 expression by Real-time PCR as well as cell invasion by Transwell assay. In HPV16 E7 group, HPV16 E7 and HOXA1 expression was significantly increased, cell proliferation was promoted, invasive ability was increased, Caspase 3 activity and Bax expression was decreased, and Bcl-2 expression was increased compared to control group (P < 0 05). Conversely, inhibition of FOXA1 expression in Hela cells overexpressing HPV16 E7 can significantly inhibit cell proliferation and invasion, and promote apoptosis (P < 0 05). HPV16 E7 protein can up-regulate FOXA1 in host cells, and promote cervical cancer cell growth, proliferation and invasion, indicating that it is one of the key factors contributing to cervical cancer.

2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.


PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53989 ◽  
Author(s):  
Fengjie Guo ◽  
Yalin Li ◽  
Jiajia Wang ◽  
Yandong Li ◽  
Yuehui Li ◽  
...  

2021 ◽  
Vol 13 (8) ◽  
pp. 1506-1511
Author(s):  
Minjuan Xu ◽  
Jun Huang ◽  
Liefeng Wang

Cervical cancer is often treated with surgery, radiotherapy and chemotherapy, but it does not have the advantages of precise treatment and prognosis is not ideal. Molecular targeted therapy can make up for the above shortcomings. This study mainly analyzed the influence of miR-126 on cervical cancer cells and possible molecular mechanisms, so as to provide a reference for better clinical improvement of prognosis for cervical cancer. C33a cells were assigned into control group, empty carrier group (C33a cells were co-cultured with liposome nanoparticle carrier), inhibitor group (C33a cells were treated with PD-1/PD-L1 signaling pathway inhibitor), miR-126 group (miR-126 with liposomal nanoparticles as carrier was added to C33a cells), followed by expression analysis of miR-126 and AK2, cell proliferation, PD-1/PD-L1 signaling and phosphorylation levels, as well as tumor mass and volume in nude mice. At 24 h, no difference of cell proliferation was found (P > 0.05) but cell proliferation showed significant differences after cell growth of 48 h, with lower proliferation in inhibitor group and miR-126 group (P < 0.05). The levels of PD-1, PD-L1, AK2, and p-PD-1 in inhibitor group and miR-126 group were significantly lower than for the other two groups (P > 0.05). There was a target relationship between miR-126 and AK2. The transplanted tumor in the miR-126 group was significantly decreased, with lower tumor mass and volume than control group (P < 0.05). The carrier-based miR-126 and PD-1/PD-L1 signaling inhibitors can inhibit cervical cancer cell proliferation.


Tumor Biology ◽  
2015 ◽  
Vol 36 (10) ◽  
pp. 8065-8073 ◽  
Author(s):  
Boya Deng ◽  
Yi Zhang ◽  
Siyang Zhang ◽  
Fang Wen ◽  
Yuan Miao ◽  
...  

Author(s):  
Nuraeni Ekowati ◽  
Aris Mumpuni ◽  
Juni Safitri Muljowati

<p><em>Pleurotus ostreatus</em> is a common mushroom cultivated in Indonesia, and potential properties of bioactive compounds for medicinal mushroom. This study was aimed at obtaining <em>P.ostreatus</em> extract bioactive compounds potential in inhibiting the proliferation of cervical cancer cells (HeLa) and evaluating the HeLa cell proliferation kinetics and HeLa cell death mechanisms. The research was beneficial in making this product can be easily applied in a more controlled industrial scale. Anticancer activity test through a cytotoxic test using the MTT [3- (4,5-dimetiltiazol-2-yl) -2.5-diphenyl tertrazolium bromide], the kinetics proliferation of HeLa cells and HeLa cell death mechanism was performed. Linear regression analysis was used to analyze the data. Ethyl acetate extract of <em>P.</em> <em>ostreatus</em> isolated from Madiun showed the best results with IC <sub>50</sub> = 107.59 µg / ml. HeLa cell proliferation kinetics analysis showed that the application of bioactive compounds 100 µg / ml resulted in an increase of in death of HeLa cells along with length of incubation time. An important finding was that HeLa cells death by apoptosis was greater than by necrosis.  In conclusion, the extracts of <em>P.</em> <em>ostreatus</em>  has the potential to inhibit the growth of HeLa cells.</p><p> </p>


2020 ◽  
Author(s):  
Kang Zhu ◽  
He Bai ◽  
Mingzhu Mu ◽  
Yuanyuan Xue ◽  
Zhao Duan

Abstract Background Given its crucial role in human malignancies, how Ring finger protein 6 (RNF6) functions in cervical cancer has yet to be elucidated. In our research, we explored the biological significance of RNF6 in cervical cancer HeLa cells and its possible regulatory mechanism. Methods The expression levels of RNF6 mRNA and protein in cervical cancer tissues and cells were both analyzed, the former by Gene Expression Profiling Interactive Analysis (GEPIA), and the latter by quantitative real-time PCR (qRT-PCR) and immunohistochemistry assays. In vitro cell proliferation was tested through MTT assay and flow cytometer was used to detected Cell apoptosis. The activation of ERK(extracellular signal regulated kinase) was explored by Western Blot. Results In the present research, we found that the expression of RNF6 was high in both primary tissues and cervical cancer cells. RNF6 could promote cervical cancer HeLa cells growth. Once knockdown of RNF6 in cervical cancer cells, cell proliferation could be suppressed and cell apoptosis was promoted. Moreover, its elevation had an adverse effect on the prognosis of cervical cancer. Further studies showed that ERK activation is one of the potential mechanisms. Conclusion These findings provided evidence that the up-regulated RNF6 could activate the MAPK/ERK pathway to regulate the cell growth in cervical cancer, which suggested that RNF6 could be a promising target for diagnosis and treatment for cervical cancer.


Author(s):  
Gizem Cocelli ◽  
◽  
Mustafa Pehlivan ◽  
Onder Yumrutas ◽  
◽  
...  

In this study, it was aimed to determine the antioxidant and anticancer activities of Sideritis perfoliata methanolic extract (SPE) on cervical cancer cells (HeLa). Different doses (25, 50, 100 and 200 µg/mL) of SPE were used to determine proliferation of HeLa cells by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) staining method. Induction of apoptosis was determined by Annexine-V and propidium iodide staining method. Interleukin (IL) 6-8 levels were measured by ELISA method. Antioxidant activities of SPE were determined by DPPH, DNA (plasmid pBR322) protecting and cellular antioxidant activity tests. Some phytochemicals of SPE were also screened by LC-MS-MS. It was determined that SPE reduced the proliferation of HeLa cells and also induced apoptosis. IL6-8 levels importantly decreased at 200 µg/mL. SPE exhibited moderately antioxidant activities in tests used. Among the phenolics identified, vanillic acid had the highest amount. As a result, it was determined to have the anticancer activity of SPE by decreasing cell proliferation, inducing apoptosis and decreasing IL6-8 in HeLa cells.


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