Co‐delivery of hypoxia inducible factor‐1α small interfering RNA and 5‐fluorouracil to overcome drug resistance in gastric cancer SGC‐7901 cells

Chen, Yunna; Sun, Li; Guo, Dongdong; Wu, Zhongzhi; Chen, Weidong

doi:10.1002/jgm.2998

Cited by 23 publications

(15 citation statements)

References 43 publications

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“…It was reported that hypoxia confers sorafenib resistance in myeloid leukemia, renal, or gastric cancer cells 35 – 38 and is responsible for the acquired resistance to different anticancer drugs in HCC cells, including doxorubicin, etoposide, cisplatin, SN38, and 5-fluorouracil 39 – 43 . In fact, Liang et al 32 reported that the continued administration of sorafenib in HCC subcutaneous mouse tumor models increases the protein levels and transcriptional activity of HIF-1α.…”

Section: Hifs and Sorafenib Resistancementioning

confidence: 99%

Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors

et al. 2018

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Sorafenib, a multikinase inhibitor with antiproliferative, antiangiogenic, and proapoptotic properties, constitutes the only effective first-line drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Despite its capacity to increase survival in HCC patients, its success is quite low in the long term owing to the development of resistant cells through several mechanisms. Among these mechanisms, the antiangiogenic effects of sustained sorafenib treatment induce a reduction of microvessel density, promoting intratumoral hypoxia and hypoxia-inducible factors (HIFs)-mediated cellular responses that favor the selection of resistant cells adapted to the hypoxic microenvironment. Clinical data have demonstrated that overexpressed HIF-1α and HIF-2α in HCC patients are reliable markers of a poor prognosis. Thus, the combination of current sorafenib treatment with gene therapy or inhibitors against HIFs have been documented as promising approaches to overcome sorafenib resistance both in vitro and in vivo. Because the depletion of one HIF-α subunit elevates the expression of the other HIF-α isoform through a compensatory loop, targeting both HIF-1α and HIF-2α would be a more interesting strategy than therapies that discriminate among HIF-α isoforms. In conclusion, there is a marked correlation between the hypoxic microenvironment and sorafenib resistance, suggesting that targeting HIFs is a promising way to increase the efficiency of treatment.

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Section: Hifs and Sorafenib Resistancementioning

confidence: 99%

Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors

et al. 2018

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“…It has also been observed that the synergistic cytotoxic potential for Chk1 inhibition during 5‑FU treatment in p53‑deficient colon cancer cells with or without 5‑FU resistance. 116 , 117 …”

Section: Different Aspects Of the Use Of Nanocarriers – Prevention Diagnostic And Therapeutic Applicationmentioning

confidence: 99%

“…It has also been observed that the synergistic cytotoxic potential for Chk1 inhibition during 5-FU treatment in p53-deficient colon cancer cells with or without 5-FU resistance. 116,117 Paclitaxel (PTX) is used against many forms of cancer, for example, ovarian, breast, lung, Kaposi sarcoma, cervical, and pancreatic cancer. Mechanism of action relates to targeting microtubules -it disrupts the major function of microtubules, which is the production of the mitotic spindle during cell division, as well as maintenance of the cell structure, motility, and cytoplasmic movement within the cell.…”

Section: The Efficiency Of Encapsulation/ Immobilization Of Drugs In Carriersmentioning

confidence: 99%

Current Trends and Challenges in Pharmacoeconomic Aspects of Nanocarriers as Drug Delivery Systems for Cancer Treatment

Milewska¹,

Niemirowicz-Laskowska²,

Siemiaszko³

et al. 2021

IJN

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Nanotherapy is a part of nanomedicine that involves nanoparticles as carriers to deliver drugs to target locations. This novel targeting approach has been found to resolve various problems, especially those associated with cancer treatment. In nanotherapy, the carrier plays a crucial role in handling many of the existing challenges, including drug protection before early-stage degradations of active substances, allowing them to reach targeted cells and overcome cell resistance mechanisms. The present review comprises the following sections: the first part presents the introduction of pharmacoeconomics as a branch of healthcare economics, the second part covers various beneficial aspects of the use of nanocarriers for in vitro, in vivo, and pre- and clinical studies, as well as discussion on drug resistance problem and present solutions to overcome it. In the third part, progress in drug manufacturing and optimization of the process of nanoparticle synthesis were discussed. Finally, pharmacokinetic and toxicological properties of nanoformulations due to up-to-date studies were summarized. In this review, the most recent developments in the field of nanotechnology’s economic impact, particularly beneficial applications in medicine were presented. Primarily focus on cancer treatment, but also discussion on other fields of application, which are strongly associated with cancer epidemiology and treatment, was made. In addition, the current limitations of nanomedicine and its huge potential to improve and develop the health care system were presented.

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“…Hypoxia contribution to chemoresistance development in HCC has been described after the administration of drugs, such as 5-fluorouracil (5-FU) [25], doxorubicin, and cisplatin [26]. Involvement of hypoxic environment in the acquired resistance to sorafenib has also been reported in renal cancer [27,28], gastric cancer [29], and acute myeloid leukaemia [30]. In samples of patients with untreated HCC sensitive and resistant to sorafenib, intratumoral hypoxia increased in patients resistant to sorafenib as opposed to sensitive ones [20].…”

Section: Discussionmentioning

confidence: 99%

Stabilization of Hypoxia-Inducible Factors and BNIP3 Promoter Methylation Contribute to Acquired Sorafenib Resistance in Human Hepatocarcinoma Cells

Méndez-Blanco

Fondevila

Fernández-Palanca

et al. 2019

Cancers

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Despite sorafenib effectiveness against advanced hepatocarcinoma (HCC), long-term exposure to antiangiogenic drugs leads to hypoxic microenvironment, a key contributor to chemoresistance acquisition. We aimed to study the role of hypoxia in the development of sorafenib resistance in a human HCC in vitro model employing the HCC line HepG2 and two variants with acquired sorafenib resistance, HepG2S1 and HepG2S3, and CoCl2 as hypoximimetic. Resistant cells exhibited a faster proliferative rate and hypoxia adaptive mechanisms, linked to the increased protein levels and nuclear translocation of hypoxia-inducible factors (HIFs). HIF-1α and HIF-2α overexpression was detected even under normoxia through a deregulation of its degradation mechanisms. Proapoptotic markers expression and subG1 population decreased significantly in HepG2S1 and HepG2S3, suggesting evasion of sorafenib-mediated cell death. HIF-1α and HIF-2α knockdown diminished resistant cells viability, relating HIFs overexpression with its prosurvival ability. Additionally, epigenetic silencing of Bcl-2 interacting protein 3 (BNIP3) was observed in sorafenib resistant cells under hypoxia. Demethylation of BNIP3 promoter, but not histone acetylation, restored BNIP3 expression, driving resistant cells’ death. Altogether, our results highlight the involvement of HIFs overexpression and BNIP3 methylation-dependent knockdown in the development of sorafenib resistance in HCC. Targeting both prosurvival mechanisms could overcome chemoresistance and improve future therapeutic approaches.

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Co‐delivery of hypoxia inducible factor‐1α small interfering RNA and 5‐fluorouracil to overcome drug resistance in gastric cancer SGC‐7901 cells

Abstract: Co-delivery of siRNA and 5-fluorouracil chitosan nanoparticles is an attractive strategy for overcoming multidrug resistance.

Cited by 23 publications

References 43 publications

Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors

Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors

Current Trends and Challenges in Pharmacoeconomic Aspects of Nanocarriers as Drug Delivery Systems for Cancer Treatment

Stabilization of Hypoxia-Inducible Factors and BNIP3 Promoter Methylation Contribute to Acquired Sorafenib Resistance in Human Hepatocarcinoma Cells

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