Synergism between RIZ1 gene therapy and paclitaxel in SiHa cervical cancer cells

Cheng, Hairong; Zhang, T; Qu, Yanlin; Shi, Wencong; Lou, Ge; Liu, Yao-Bin; Zhang, Y Y; Cheng, Li

doi:10.1038/cgt.2016.44

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…Paclitaxel (Figure 1) is widely known to specifically interact with tubulins and is one of the first line treatments for ovarian and breast cancer [40,41]. In this context, we used Paclitaxel as a standard and found that it affected HeLa and CaSki at a concentration of 0.19 μM at 48 h of exposure.…”

Section: Resultsmentioning

confidence: 98%

Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines

et al. 2019

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A series of 12 polysubstituted pyrrolo[3,4-b]pyridin-5-ones were synthesized via a one-pot cascade process (Ugi–3CR/aza Diels-Alder/N-acylation/decarboxylation/dehydration) and studied in vitro using human epithelial cervical carcinoma SiHa, HeLa, and CaSki cell line cultures. Three compounds of the series exhibited significative cytotoxicity against the three cell lines, with HeLa being the most sensitive one. Then, based on these results, in silico studies by docking techniques were performed using Paclitaxel as a reference and αβ-tubulin as the selected biological target. Worth highlighting is that strong hydrophobic interactions were observed between the three active molecules and the reference drug Paclitaxel, to the αβ-tubulin. In consequence, it was determined that hydrophobic–aromatic moieties of bioactive compounds and Paclitaxel play a key role in making stronger interactions to the ligand–target complex. A quantitative structure activity relationship (QSAR) study revealed that the six membered rings are the most significant molecular frameworks, being present in all proposed models for the in vitro-studied cell lines. Finally, also from the docking interpretation, a ligand-based pharmacophore model is proposed in order to find further potential polyheterocyclic candidates to bind stronger to the αβ-tubulin.

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Section: Resultsmentioning

confidence: 98%

Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines

et al. 2019

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“…Thus, the use of only the C33a cell line-which is negative for HPV DNA and RNA-as an experimental model is not enough and cannot be considered a representative study sample, taking into account the cellular Another tumor suppressor gene studied in cervical cancer is retinoblastoma protein zinc finger gene (RIZ), specifically its RIZ1 expression products, which can induce cell cycle arrest and apoptosis. Cheng et al found the upregulation of RIZ1 in SiHa(HPV16+ve) cells reduced cell proliferation, and treatment with PTX increased the expression level of RIZ1 and enhanced tumor suppressive function, indicating that RIZ1 combined with PTX has a synergic effect [40]. The same group also found that RIZ1 overexpression combined with RT achieved an increased apoptosis rate and DNA damage in HeLa and SiHa cells, with an enhanced radiosensitivity of cancer cells [41].…”

Section: Tumor Suppressor Gene Restorationmentioning

confidence: 98%

Targeted Gene Delivery Therapies for Cervical Cancer

Ayén

Martínez

Boulaiz

2020

Cancers

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Despite being largely preventable through early vaccination and screening strategies, cervical cancer is the most common type of gynecological malignancy worldwide and constitutes one of the leading causes of cancer deaths in women. Patients with advanced or recurrent disease have a very poor prognosis; hence, novel therapeutic modalities to improve clinical outcomes in cervical malignancy are needed. In this regard, targeted gene delivery therapy is presented as a promising approach, which leads to the development of multiple strategies focused on different aspects. These range from altered gene restoration, immune system potentiation, and oncolytic virotherapy to the use of nanotechnology and the design of improved and enhanced gene delivery systems, among others. In the present manuscript, we review the current progress made in targeted gene delivery therapy for cervical cancer, the advantages and drawbacks and their clinical application. At present, multiple targeted gene delivery systems have been reported with encouraging preclinical results. However, the translation to humans has not yet shown a significant clinical benefit due principally to the lack of efficient vectors. Real efforts are being made to develop new gene delivery systems, to improve tumor targeting and to minimize toxicity in normal tissues.

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“…Another tumour suppressor gene with clinical importance in cervical cancer gene therapy is the retinoblastoma protein zinc finger gene 1 (RIZ1) since it can induce apoptosis and cell cycle arrest. Cheng et al demonstrated that overexpression of RIZ1 expression in HPV16-positive cervical cancer cells could lead to impaired cell proliferation and increased apoptosis [131]. When this overexpression is combined with radiotherapy, it leads to increased apoptosis and DNA damage in HeLa and SiHa cells [146].…”

Section: Plasmidsmentioning

confidence: 99%

Gene Therapy for Malignant and Benign Gynaecological Disorders: A Systematic Review of an Emerging Success Story

Drakopoulou

Anagnou

Pappa

2022

Cancers

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Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women’s life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach.

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Synergism between RIZ1 gene therapy and paclitaxel in SiHa cervical cancer cells

Cited by 9 publications

References 31 publications

Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines

Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines

Targeted Gene Delivery Therapies for Cervical Cancer

Gene Therapy for Malignant and Benign Gynaecological Disorders: A Systematic Review of an Emerging Success Story

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