Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

Wang, Feng; Tang, Jinyuan; Li, Pengchao; Si, Shuhui; Yu, Hao; Yang, Xiao; Tao, Jun; Lv, Qiang; Gu, Min; Yang, Haiwei; Wang, Zengjun

doi:10.1159/000486222

Cited by 86 publications

(65 citation statements)

References 36 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They are believed to inhibit lysosome-dependent autophagy and improve chemo and radio sensitivity [76]. Some of the most recent publications on this matter included breast cancer [77], pancreatic cancer [78,79], lung cancer [80], colon cancer [81], and bladder cancer [82].…”

Section: Quinolines: Chloroquine and Quinidinementioning

confidence: 99%

In Search of a Breakthrough Therapy for Glioblastoma Multiforme

Vasilev

Sofi

et al. 2018

Neuroglia

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is an extremely malignant type of brain cancer which originates from astrocytes or their precursors. Glioblastoma multiforme cells share some features with astrocytes but are characterized by highly unstable genomes with multiple driver mutations and aberrations. Effective therapies for GBM are lacking and hardly any progress has been made in the last 15 years in terms of improving the outcomes for patients. The lack of new especially targeted anti-GBM medications has prompted scientists in academia around the world to test whether any of the currently approved drugs might be used to fight this devastating disease. This approach is known as repurposing. Dozens of drugs have been reported to have anti-GBM properties in vitro but there is no solid evidence for the clinical efficacy of any of them. Perhaps the most interesting group of those repurposed are tricyclic antidepressants but the mechanism of their action on GBM cells remains obscure. In this brief review we consider various approaches to repurpose drugs for therapy of GBM and highlight their limitations. We also pay special attention to the mitochondria, which appear to be intimately involved in the process of apoptosis and could be a focus of future developments in search of a better treatment for patients suffering from GBM.

show abstract

Section: Quinolines: Chloroquine and Quinidinementioning

confidence: 99%

In Search of a Breakthrough Therapy for Glioblastoma Multiforme

Vasilev

Sofi

et al. 2018

Neuroglia

View full text Add to dashboard Cite

show abstract

“…To overcome radioresistance and increase survival, many attempts have been made to develop new radiosensitizers [15][16][17][18]. Recent studies revealed that ultrasound-stimulated microbubbles (USMBs) induced vessel destruction in tumors [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-Stimulated Microbubbles Enhance Radiosensitization of Nasopharyngeal Carcinoma

Deng

Cai

Feng

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Recent studies indicate that therapies targeting the vasculature can significantly sensitize tumors to radiation. Ultrasound-stimulated microbubbles (USMBs) are regarded as a promising radiosensitizer. In this study, we investigated the effect of USMBs on the sensitivity of nasopharyngeal carcinoma (NPC) to radiation. Methods: Human NPC (CNE-2) cells and human umbilical vein endothelial cells (HUVECs) were exposed to radiation (0, 2, and 8 Gy) alone or in combination with USMBs. Cell viability and apoptosis were measured with the MTT assay and flow cytometry, respectively. The angiogenic activity of HUVECs was detected using matrigel tubule formation. The in vitro effects induced by these treatments were confirmed in vivo with xenograft models of CNE-2 cells in nude mice by examining vascular integrity using color Doppler flow imaging and cell survival using immunohistochemistry. Additionally, the in vivo and in vitro expressions of angiotensin II (ANG II) and its receptor (AT1R) were detected by immunohistochemistry and western blotting, respectively. With CNE-2 cells and HUVECs transfected with control, ANG II, or AT1R, perindopril (an inhibitor of angiotensin-converting enzyme) and candesartan (an inhibitor of AT1R) were used to verify the role of ANG II and AT1R in the radiosensitivity of tumor and endothelial cells by USMBs, by determining cell viability and apoptosis and angiogenic activity. Results: In the NPC xenografts, USMBs slightly reduced blood flow and CD34 expression, increased tumor cell death and ANG II and AT1R expression, and significantly enhanced the effects of radiation. With CNE-2 cells and HUVECs, the USMBs further enhanced the inhibition of tumor cell viability and endothelial tubule formation and further enhanced the increase in ANG II and AT1R due to radiation. Furthermore, perindopril and candesartan significantly enhanced the inhibitory effect of radiation and USMBs on tumor cell growth and angiogenesis in vitro. Conclusions: We have demonstrated for the first time that USMB exposure can significantly enhance the destructive effect on NPC of radiation, and this effect might be further increased by ANG II and AT1R inhibition. Our findings suggest that USMBs can be used as a promising sensitizer of radiotherapy to treat NPC, and the clinical effect might be increased by ANG II and AT1R inhibition.

show abstract

“…Furthermore, more and more evidences have con rmed the existence of autophagy is the basic mechanism of cell survival in stressful environments caused by radiotherapy and chemotherapy. The increase of autophagy will enhance the radioresistance of tumor, and tumor with autophagy defect are more sensitive to radiotherapy [45].…”

Section: Discussionmentioning

confidence: 99%

Silencing VEGF enhances the radiosensitivity of the radioresistant human nasopharyngeal carcinoma cell line CNE-2R by inhibiting autophagy through the activation of mTOR pathway

Chen

Lin

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. VEGF was reported to promote the occurrence of autophagy, which enhanced to the radioresistance of tumors. The purpose of our study was to investigate the influence of VEGF silencing on the radiosensitivity of nasopharyngeal carcinoma radioresistant cell line CNE-2R and the underlying mechanisms.Methods: The radiosensitivity of CNE-2R cells after silencing VEGF was detected by cell counting kit 8 (CCK-8) and clonogenic assay, cell cycle and apoptosis was subjected to flow cytometry. DNA damage and autophagy were observed by immunofluorescence and western blotting. The interaction between VEGF and mTOR was confirmed by western blotting and co-immunoprecipitation analysis. In vivo, the effect of VEGF on radiosensitivity of NPC cells was investigated through xenograft model, furthermore, immunohistochemistry and TUNEL assay were used to further verify the relationship between autophagy and radiosensitivity in NPC after VEGF depletion.Results: Downregulation of VEGF significantly inhibited cell proliferation and induced apoptosis of CNE-2R cells after radiotherapy in vitro and in vivo. In addition, VEGF knockdown not only decreased autophagy level, but also delayed the DNA damage repair in CNE-2R cells after irradiation. Mechanistically, silencing VEGF suppressed autophagy through the activation of mTOR pathway.Conclusion: VEGF depletion increased radiosensitivity of NPC radioresistant cell CNE-2R by suppressing autophagy via the activation of mTOR pathway.

show abstract

Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

Cited by 86 publications

References 36 publications

In Search of a Breakthrough Therapy for Glioblastoma Multiforme

In Search of a Breakthrough Therapy for Glioblastoma Multiforme

Ultrasound-Stimulated Microbubbles Enhance Radiosensitization of Nasopharyngeal Carcinoma

Silencing VEGF enhances the radiosensitivity of the radioresistant human nasopharyngeal carcinoma cell line CNE-2R by inhibiting autophagy through the activation of mTOR pathway

Contact Info

Product

Resources

About