scholarly journals Somatic mutations and CRISPR/Cas9 library screening integrated analysis identifies cervical cancer drug‐resistant pathways

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Chen Cao ◽  
Ting Liu ◽  
Qinghua Zhang ◽  
Rui Li ◽  
Zhen Zeng ◽  
...  
Author(s):  
Muhammad Hasan Bashari ◽  
Fachreza Aryo Damara ◽  
Isna Nisrina Hardani ◽  
Gita Widya Pradini ◽  
Tenny Putri ◽  
...  

Cervical cancer is one of the most leading causes of women death. Currently, paclitaxel is still one of the main therapeutic regimens for cervical cancer patients. However, some patients developed to be paclitaxel-resistant. Hence, studies to find out the novel strategies to resolve this problem are important. Generating resistant cancer cell lines can be utilized as the potent tool to evaluate the efficacy of any therapeutic agent toward cancer drug-resistant problems. Current studies describing the methods to establish chemoresistance are lacking. Moreover, study in Indonesia conducting chemoresistance in cell line is limited. This study was aimed to elaborate the characteristics of HeLa cells during generation of paclitaxel-resistant cervical cancer cells. The parental HeLa cells were exposed to an escalating concentration of paclitaxel for a long time period. Subsequently, cells were divided into two groups for the evaluation of resistance characteristics. The values of inhibitory concentration 50 (IC50) and inhibitory concentration 90 (IC90) were analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Our data showed that the longer exposing periods of paclitaxel, the higher IC50 and IC90 values of HeLa cells are. IC90 of paclitaxel in HeLa Pac RB was increased from 69 pM, 440 pM, 2,561 pM and 10,337 pM on 0th, 1st, 2nd, 3rd and 4th months, respectively. Interestingly, the resistant cells were recovered to be paclitaxel-sensitive when they were not being continuously exposed to paclitaxel. In addition, the paclitaxel resistant cells become less sensitive against 5-FU but not doxorubicin, cisplatin and etoposide. We were able to generate cervical cancer HeLa paclitaxel-resistant cell line. These cell line could potentially be utilized for further studies in order to understand the molecular mechanisms of drug resistance in cervical cancer and as a tool for cancer drug discovery.Keywords: cervical cancer, drug resistant cell line, paclitaxel resistant cells, stepwise escalating concentration.


2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 654
Author(s):  
Vellingiri Manon Mani ◽  
Arockiam Jeyasundar Parimala Gnana Soundari ◽  
Balamuralikrishnan Balasubramanian ◽  
Sungkwon Park ◽  
Utthapon Issara ◽  
...  

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.


Oncotarget ◽  
2017 ◽  
Vol 8 (43) ◽  
pp. 74466-74478 ◽  
Author(s):  
Andrzej Klejewski ◽  
Karolina Sterzyńska ◽  
Karolina Wojtowicz ◽  
Monika Świerczewska ◽  
Małgorzata Partyka ◽  
...  

2018 ◽  
Vol 149 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Long Chen ◽  
Shaohong Luan ◽  
Baoguo Xia ◽  
Yansheng Liu ◽  
Yuan Gao ◽  
...  

Author(s):  
Syafruddin Ilyas ◽  
Rostime H. Simanullang ◽  
Salomo Hutahaean ◽  
Rosidah Rosidah ◽  
Putri C. Situmorang

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.


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