Oncolytic adenoviral H101 synergizes with radiation in cervical cancer cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Yixin Duan ◽  
Haixia Bai ◽  
Xiang Li ◽  
Depu Wang ◽  
Yin Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Viral Load ◽  
Combination Therapy ◽  
Cell Viability ◽  
Cancer Cells ◽  
P53 Protein ◽  
Combined Treatment ◽  
High Dose ◽  
Hpv16 E6 ◽  
Cervical Cancer Cells

Background: : A major challenge in cervical cancer radiotherapy is to tailor the radiation doses efficiently to both eliminate malignant cells and to reduce the side effects to normal tissue. Oncolytic adenoviral drug H101 is recently tested and approved for topical adjuvant treatment of several malignancies. Objective: This study is to evaluate the potential neoadjuvant radiotherapy benefits of H101 by testing the inhibitory function of H101 combined with radiation in different cervical cancer cells. Methods: Human cervical cancer cells C33a, SiHa, CaSki, and Hela were treated with varying concentrations of H101 alone or combined with radiation (2Gy or 4Gy). Cell viability and apoptosis were measured at indicated time intervals. HPV16 E6 and cellular p53 mRNA expression alteration were measured by qRT-PCR. RNA scope in-situ detect HPV E6 status. P53 protein alteration are detected by Western blot. Results: Cell viability and apoptosis show the combination of a high dose of H101 (MOI=1000, 10000) with radiation yielded a synergistic anti-cancer effect in all tested cervical cancer cell lines (P<0.05), with the greatest effect achieved in HPV negative C33a cells (P<0.05). Low HPV16 viral load SiHa cell was more sensitive to combination therapy than high HPV16 viral load CaSki cell (P<0.05). The combined treatment could reduce HPV16 E6 expression and increase cellular P53 level compared to radiation alone in SiHa and CaSki (P<0.05). Conclusions: Oncolytic adenoviral H101 effectively enhances the antitumor efficacy of radiation in cervical cancer cells and may serve as a novel combination therapy for cervical cancer.

scholarly journals The Application of Arsenic Trioxide in Ameliorating ABT-737 Target Therapy on Uterine Cervical Cancer Cells through Unique Pathways in Cell Death

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 108 ◽  
Author(s):  
I-Lun Hsin ◽  
Ying-Hsiang Chou ◽  
Wei-Li Hung ◽  
Jiunn-Liang Ko ◽  
Po-Hui Wang
Keyword(s):  
Cervical Cancer ◽  
Synergistic Effect ◽  
Cancer Cells ◽  
Arsenic Trioxide ◽  
Combination Treatment ◽  
Combined Treatment ◽  
B Cell Lymphoma ◽  
Uterine Cervical Cancer ◽  
Cervical Cancer Cells ◽  
Mediated Reduction

ABT-737, a B cell lymphoma-2 (Bcl-2) family inhibitor, activates apoptosis in cancer cells. Arsenic trioxide is an apoptosis activator that impairs cancer cell survival. The aim of this study was to evaluate the effect of a combination treatment with ABT-737 and arsenic trioxide on uterine cervical cancer cells. MTT (3-(4,5-dimethylthiazol-2-yl)-25-diphenyltetrazolium bromide) assay revealed that ABT-737 and arsenic trioxide induced a synergistic effect on uterine cervical cancer cells. Arsenic trioxide enhanced ABT-737-induced apoptosis and caspase-7 activation and the ABT-737-mediated reduction of anti-apoptotic protein Mcl-1 in Caski cells. Western blot assay revealed that arsenic trioxide promoted the ABT-737-mediated reduction of CDK6 and thymidylate synthetase in Caski cells. Arsenic trioxide promoted ABT-737-inhibited mitochondrial membrane potential and ABT-737-inhibited ANT expression in Caski cells. However, ABT-737-elicited reactive oxygen species were not enhanced by arsenic trioxide. The combined treatment induced an anti-apoptosis autophagy in SiHa cells. This study is the first to demonstrate that a combination treatment with ABT-737 and arsenic trioxide induces a synergistic effect on uterine cervical cancer cells through apoptosis. Our findings provide new insights into uterine cervical cancer treatment.

scholarly journals Inhibition of Kpn β 1 Mediated Nuclear Import Enhances Cisplatin Chemosensitivity in Cervical Cancer.

2020 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Pauline van der Watt ◽  
Wei Wei ◽  
Michael Birrer ◽  
Virna Leaner
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cell Viability ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Nuclear Import ◽  
Reporter Activity ◽  
Cervical Cancer Cells ◽  
Cisplatin Sensitivity ◽  
Pre Treatment

Abstract Background: Inhibition of nuclear import via Karyopherin beta 1 (Kpnβ1) shows potential as an anti-cancer approach. This study investigated the use of nuclear import inhibitor, INI-43, in combination with cisplatin. Methods: Cervical cancer cells were pre-treated with INI-43 before treatment with cisplatin, and MTT cell viability and apoptosis assays performed. Activity and localisation of p53 and NFκB was determined after co-treatment of cells.Results: Pre-treatment of cervical cancer cells with INI-43 at sublethal concentrations enhanced cisplatin sensitivity, evident through decreased cell viability and enhanced apoptosis. Kpnβ1 knock-down cells similarly displayed increased sensitivity to cisplatin. Combination index determination using the Chou-Talalay method revealed that INI-43 and cisplatin engaged in synergistic interactions. p53 was found to be involved in the cell death response to combination treatment as its inhibition abolished the enhanced cell death observed. INI-43 pre-treatment resulted in moderately stabilized p53 and induced p53 reporter activity, which translated to increased p21 and decreased Mcl-1 upon cisplatin combination treatment. Furthermore, cisplatin treatment led to nuclear import of NFκB, which was diminished upon pre-treatment with INI-43. NFκB reporter activity and expression of NFκB transcriptional targets, cyclin D1, c-Myc and XIAP, showed decreased levels after combination treatment compared to single cisplatin treatment and this associated with enhanced DNA damage. Conclusions: Taken together, this study shows that INI-43 pre-treatment significantly enhances cisplatin sensitivity in cervical cancer cells, mediated through stabilization of p53 and decreased nuclear import of NFκB. Hence this study suggests the possible synergistic use of nuclear import inhibition and cisplatin to treat cervical cancer.

scholarly journals Physcion Induces Potential Anticancer Effects in Cervical Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2029
Author(s):  
Wojciech Trybus ◽  
Teodora Król ◽  
Ewa Trybus ◽  
Anna Stachurska
Keyword(s):  
Electron Microscopy ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cervical Cancer ◽  
Protein Expression ◽  
Cell Viability ◽  
Cancer Cells ◽  
Oxygen Species ◽  
Test Compound ◽  
Cervical Cancer Cells

Background: The extent of morphological and ultrastructural changes in HeLa cells was assessed by optical, fluorescence and electron microscopy after exposure to various concentrations of physcion, taking into account the biological properties of the test compound. Methods: Cell viability was assessed by MTT assay, while the cell cycle, LC3 expression, apoptosis, change of mitochondrial potential, Bcl-2 protein expression level and the level of reactive oxygen species were analyzed by flow cytometry. Results: As a result of physcion encumbrance, concentration-dependent inhibition of HeLa cell viability and the G0/G1 phase of the cell cycle was observed. Activation of the lysosomal system was also revealed, which was expressed by an increased number of lysosomes, autophage vacuoles and increased expression of the LC3 protein, a marker of the autophagy process. Transmission electron microscopy and fluorescence microscopy showed that physcion induced clear changes in cervical cancer cells, especially in the structure of the nucleus and mitochondria, which correlated with the production of reactive oxygen species by the test compound and indicated the induction of the oxidative process. At the same time, the pro-apoptotic effect of physcion was demonstrated, and this mechanism was dependent on the activation of caspases 3/7 and the reduction in Bcl-2 protein expression. Conclusion: The obtained results indicate an antitumor mechanism of action of physcion, based on the induction of oxidative stress, autophagy and apoptosis.

Sevoflurane Inhibits Growth and Metastasis of Cervical Cancer Through Up-Regulating miR-203 by Targeting Tumor Protein Translationally Controlled 1

2020 ◽  
Vol 10 (6) ◽  
pp. 874-883
Author(s):  
Li Zhang ◽  
Shiyou Wei ◽  
Zhenkai Xu ◽  
Wen Sun ◽  
Lihua Hang
Keyword(s):  
Cervical Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter System ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis ◽  
Cancer Tissues

Background: Cervical cancer is a type of malignancy with high incidence and high mortality in women all over the world. Recent findings revealed the role of sevoflurane in the inhibition of development of various cancer types. This study aimed to explore whether sevoflurane could suppress cells proliferation and metastasis through adjusting miR-203 expression in cervical cancer. Methods: The effects of sevoflurane on HeLa cell viability was assessed using CCK-8 assay. miR-203 level in Hela cells was determined by qRT-PCR. In addition, cells apoptosis, migration and invasion were evaluated using flow cytometry and transwell analysis respectively after sevoflurane treatment or miR-203 expression changes. Bioinformatics software (TargetScan) was used to predict the potential target genes for miR-203 and the prediction was validated using dual-luciferase reporter system. Results: Sevoflurane effectively inhibited cell viability, metastasis and stimulated apoptosis in cervical cancer. miR-203 demonstrated a low expression in cervical cancer tissues and cells and sevoflurane significantly up-regulated miR-203 expression in cervical cancer cells. Upregulation of miR-203 significantly suppressed cell growth and metastasis and induced apoptosis, while down-regulation of miR-203 presented the opposite effects in cervical cancer cells. In addition, the inhibitory effects of sevoflurane were eliminated by down-regulating miR-203 in cervical cancer cells. In addition, TPT1 was confirmed as a target gene for miR-203. Conclusion: Sevoflurane inhibited cervical cancer cells viability and metastasis through up-regulation of miR-203 expression by targeting TPT1.

scholarly journals Disruption of repressive p130–DREAM complexes by human papillomavirus 16 E6/E7 oncoproteins is required for cell-cycle progression in cervical cancer cells

2011 ◽  
Vol 92 (11) ◽  
pp. 2620-2627 ◽  
Author(s):  
Nurshamimi Nor Rashid ◽  
Rohana Yusof ◽  
Roger J. Watson
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Human Papillomaviruses ◽  
G1 Arrest ◽  
Cycle Progression ◽  
Hpv16 E6 ◽  
Cervical Cancer Cells ◽  
E6 And E7

Human papillomaviruses (HPVs) with tropism for mucosal epithelia are the major aetiological factors in cervical cancer. Most cancers are associated with so-called high-risk HPV types, in particular HPV16, and constitutive expression of the HPV16 E6 and E7 oncoproteins is critical for malignant transformation in infected keratinocytes. E6 and E7 bind to and inactivate the cellular tumour suppressors p53 and Rb, respectively, thus delaying differentiation and inducing proliferation in suprabasal keratinocytes to enable HPV replication. One member of the Rb family, p130, appears to be a particularly important target for E7 in promoting S-phase entry. Recent evidence indicates that p130 regulates cell-cycle progression as part of a large protein complex termed DREAM. The composition of DREAM is cell cycle-regulated, associating with E2F4 and p130 in G0/G1 and with the B-myb transcription factor in S/G2. In this study, we addressed whether p130–DREAM is disrupted in HPV16-transformed cervical cancer cells and whether this is a critical function for E6/E7. We found that p130–DREAM was greatly diminished in HPV16-transformed cervical carcinoma cells (CaSki and SiHa) compared with control cell lines; however, when E6/E7 expression was targeted by specific small hairpin RNAs, p130–DREAM was reformed and the cell cycle was arrested. We further demonstrated that the profound G1 arrest in E7-depleted CaSki cells was dependent on p130–DREAM reformation by also targeting the expression of the DREAM component Lin-54 and p130. The results show that continued HPV16 E6/E7 expression is necessary in cervical cancer cells to prevent cell-cycle arrest by a repressive p130–DREAM complex.

MicroRNA-143 Sensitizes Cervical Cancer Cells to Cisplatin: a Promising Anticancer Combination Therapy

2021 ◽  
Author(s):  
Yalda Baghay Esfandyari ◽  
Mohammad Amin Doustvandi ◽  
Mohammad Amini ◽  
Behzad Baradaran ◽  
Sheyda Jodeiry Zaer ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Cervical Cancer Cells

scholarly journals Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

2018 ◽  
Vol 46 (1) ◽  
pp. 322-334 ◽  
Author(s):  
Chia-Liang Lin ◽  
Chien-Hsing Lee ◽  
Chien-Min Chen ◽  
Chun-Wen Cheng ◽  
Pei-Ni Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Cell Viability ◽  
Er Stress ◽  
Cancer Cells ◽  
Cervical Cancer Cells ◽  
Stress Dependent ◽  
Human Cervical Cancer Cells ◽  
Human Cervical Cancer

Background/Aims: Protodioscin (PD) is a steroidal saponin with anti-cancer effects on a number of cancer cells, but the anti-tumor effects and mechanism of action of PD on human cervical cancer cells is unclear. Methods: We determined cell viability using the MTT assay. Cell death, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress were measured on a flow cytometry. Caspase activation, ER stress, and MMP-dependent apoptosis proteins in cervical cancer cells in response to PD were determined by Western blot analysis. The ability of ATF4 binding to ChIP promoter was measured using the ChIP assay. Results: We demonstrated that PD inhibits cell viability, causes a loss of mitochondrial function, and induces apoptosis, as evidenced by up-regulation of caspase-8, -3, -9, -PARP, and Bax activation, and down-regulation of Bcl-2 expression. PD was shown to induce ROS and the ER stress pathway, including GRP78, p-eIF-2α, ATF4, and CHOP. Pre-treatment with NAC, a ROS production inhibitor, significantly reduced ER stress and apoptosis-related proteins induced by PD. Transfection of GRP78/CHOP-siRNA effectively inhibited PD-induced ER stress-dependent apoptosis. Moreover, treatment with PD significantly increased p38 and JNK activation. Co-administration of a JNK inhibitor (SP600125) or p38 inhibitor (SB203580) abolished cell death and ER stress effects during PD treatment. In addition, PD induced the expression of nuclear ATF4 and CHOP, as well as the binding ability of ATF4 to the CHOP promoter. Conclusion: Our results suggest that PD is a promising therapeutic agent for the treatment of human cervical cancer.

scholarly journals HPV16 E6 regulates the proliferation, invasion, and apoptosis of cervical cancer cells by downregulating miR-504

2020 ◽  
Vol 9 (12) ◽  
pp. 7588-7595
Author(s):  
Lina Zhang ◽  
Yiqing Lai ◽  
Yangyang Sun ◽  
Baozhen Xu ◽  
Xian Qiang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Hpv16 E6 ◽  
Cervical Cancer Cells

scholarly journals ANTICANCER EFFECTS OF RETINOIC ACID IN CERVICAL CANCER CELLS

2019 ◽  
Vol 81 (2) ◽  
Author(s):  
Sugania Malar Chinapayan ◽  
Praseetha Prabhakaran
Keyword(s):  
Cervical Cancer ◽  
Stem Cell ◽  
Retinoic Acid ◽  
Cell Viability ◽  
Cancer Cells ◽  
Hela Cells ◽  
Stem Cell Markers ◽  
Anticancer Effect ◽  
Cervical Cancer Cells ◽  
Differentiation Marker

Cervical cancer is a leading cause of cancer-related death in women, and it is known to have a poor prognosis. This is because, patients develop progressive or recurrent tumours after primary treatment, and the major reason for tumour recurrence is the presence of cancer stem cells (CSCs). It is known that retinoic acid (RA) has potential therapeutic effects on cervical cancer. However, the possible mode of action of RA in cervical cancer cells, and its relation to CSCs remains elusive. The aim of this research was to determine the anticancer effect of RA in cervical cancer cells (HeLa). HeLa cells were treated by various concentrations of RA ranging from 5-50µM to determine the effect of RA on cell viability, and cell proliferation. Both experiments were carried out using Celltiter-glo 2.0 assay and CyQuant NF assay, respectively. Apoptosis activity was determined using Caspase-Glo 3/7 assay. Immunofluorescent staining was conducted to detect the expression of differentiation marker (pan-keratin), and stem cell markers (CD133 and SSEA4) on untreated and treated HeLa cells with 10µM of RA. The findings showed that RA reduced cell viability and proliferation in a dose-dependent manner by 12-83% and 22-86%, respectively. However, a change in caspase3/7 activity between untreated, and 10µM RA-treated Hela cells were not detected indicating absence of apoptotic activity. The study also revealed that expression of differentiation marker (pan-keratin) was up-regulated, while expressions of stem cell markers (CD133 and SSEA4) were down-regulated. In addition, morphology of HeLa cells displayed a more differentiated phenotype that is less proliferative upon RA treatment. These findings suggest that RA showed its anticancer effect on cervical cancer cells by exhibiting cytotoxicity, inhibiting proliferation capacity, and inducing differentiation of cervical cancer cells. This finding shows that retinoic acid may potentially serve as a potent targeted therapy for cervical cancer and other cancers possessing CSCs within its tumors.  

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