All-trans retinoic acid enhances bystander effect of suicide gene therapy in the treatment of breast cancer

Kong, Heng; Liu, Xia; Lü, Yang; Qin, Ke; Zhang, Haoyun; Zhang, Jingwen; Huang, Zong-hai; Wang, Hongxian

doi:10.3892/or.2015.4535

Cited by 25 publications

(15 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vivo studies also suggested gap junctions promoted the bystander effect and enhanced ganciclovir therapy 206 . A number of articles substantiated the role of GJIC in the bystander effect 207-211 , including very recent studies in breast cancer 212 , although some studies reported little or no effect 213 . Conversely, it was proposed 214 that HSV-TK transduced cells could be significantly protected from cell death by neighbouring cells via GJIC, possibly through the dilution of ganciclovir (or activated ganciclovir) or by the sharing of survival signals (the so-called “Good Samaritan effect”).…”

Section: Therapeutic Potentialmentioning

confidence: 99%

Gap junctions and cancer: communicating for 50 years

et al. 2016

View full text Add to dashboard Cite

Fifty years ago, tumour cells were found to lack electrical coupling, leading to the hypothesis that loss of direct intercellular communication is commonly associated with cancer onset and progression. Subsequent studies linked this phenomenon to gap junctions composed of connexin proteins. While many studies support the notion that connexins are tumour suppressors, recent evidence suggests that, in some tumour types, they may facilitate specific stages of tumour progression through both junctional and non-junctional signalling pathways. This Timeline article highlights the milestones connecting gap junctions to cancer, and underscores important unanswered questions, controversies and therapeutic opportunities in the field.

show abstract

Section: Therapeutic Potentialmentioning

confidence: 99%

Gap junctions and cancer: communicating for 50 years

et al. 2016

View full text Add to dashboard Cite

show abstract

“…It is possible that one explanation for these discrepancies is the GJ-mediated transmission of the 'death signal' from apoptotic cells to neighboring viable cells. This strategy, which is followed in GJIC-based therapies, depends on the so-called 'bystander effect' (BE) (43,44). The BE, a mechanism where a cytotoxic signal is transferred from targeted cells to neighboring cells, has been considered as an important therapeutic method (45).…”

Section: A B Discussionmentioning

confidence: 99%

Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

Jiang

Dong

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Gap junctions (GJs) serve the principal role in the antineoplastic (cytotoxicity and induced apoptosis) effect of chemical drugs. The aim of the present study was to determine the effect of GJ intercellular communication (GJIC) composed of connexin 43 (Cx43) on adriamycin cytotoxicity in breast cancer cells. Four cell lines (Hs578T, MCF-7, MDA-MB-231 and SK-BR-3) with different degree of malignancy were used in the study. The results of western blotting and immunofluorescence revealed that, in Hs578T and MCF-7 cells, which have a low degree of malignancy, the expression levels of Cx43 and GJIC were higher than those in MDA-MB-231 and SK-BR-3 cells (which have a high degree of malignancy). In Hs578T and MCF-7 cells, where GJ could be formed, the function of GJ was modulated by a pharmacological potentiators [retinoid acid (RA)]/inhibitors [oleamide and 18-α-glycyrrhetinic acid (18-α-GA)] and small interfering RNA (siRNA). In high-density cells (where GJ was formed), enhancement of GJ function by RA increased the cytotoxicity of adriamycin, while inhibition of GJ function by oleamide/18-α-GA and siRNA decreased the cytotoxicity caused by adriamycin. Notably, the modulation of GJ did not affect the survival of cells treated with adriamycin when cells were in low density (no GJ was formed). The present study illustrated the association between GJIC and the antitumor effect of adriamycin in breast cancer cells. The cytotoxicity of adriamycin on breast cancer cells was increased when the function of gap junctions was enhanced.

show abstract

“…therapeutic potential in breast cancer, colorectal cancer, and gastric cancer (39)(40)(41). However, little research exists investigating the relationship between ATRA and NPC.…”

Section: Ra Is a Metabolic Intermediate Of Vitamin A And Atramentioning

confidence: 99%

APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling

Liu¹,

Liu²,

Chen³

et al. 2019

The FASEB Journal

View full text Add to dashboard Cite

The apelin receptor (APLNR) is a GPCR involved in many pathophysiological processes; however, the correlation between APLNR expression and nasopharyngeal carcinoma (NPC) has not been reported. In this study, we used cDNA microarray data to determine APLNR expression levels in NPC tissues. We found that APLNR expression was reduced in NPC tissues compared with noncancerous nasopharyngeal epithelial tissues. Subsequently, a large‐scale sample of 1015 tissues was used to validate this discovery and explore the relationship between APLNR expression and prognosis of NPC. Expression levels of APLNR in NPC tissues were indeed down‐regulated. Furthermore, positive expression of APLNR in NPC predicted a better prognosis (disease‐free survival: P = 0.001; overall survival: P < 0.001). Moreover, ingenuity pathway analysis revealed that an indirect interaction existed between APLNR and retinoic acid (RA) in the cancer regulatory network. Consistently, after treatment with all‐trans‐RA (ATRA), we found that APLNR was significantly up‐regulated in NPC cell lines (5‐8F and HNE1), and proliferation of NPC cells was inhibited. Cell cycle arrest occurred in the G0/G1 phase. In contrast, knockdown of APLNR diminished ATRA‐induced growth inhibition of NPC cells. In addition, we surprisingly found that APLNR also played an important role in migration and invasion of NPC. Wound‐healing and Transwell assays revealed that APLNR overexpression led to reduced migratory and invasive properties in 2 NPC cell lines. Western blot results revealed that hallmarks of epithelial‐mesenchymal transition (EMT) were altered as well, suggesting that APLNR was capable of inhibiting EMT in NPC cells. Our study further demonstrated that low expression of APLNR promoted EMT in NPC cells by activating the PI3K‐protein kinase B‐mammalian target of rapamycin signaling pathway. Taken together, our data suggest that APLNR could potentially predict prognosis for patients with NPC and inhibit proliferation, migration, invasion, and EMT in nasopharyngeal cancer cells.—Liu, Y., Liu, Q., Chen, S., Liu, Y., Huang Y., Chen, P., Li, X., Gao, G., Xu, K., Fan, S., Zeng Z., Xiong W., Tan, M., Li, G., Zhang W. APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling. FASEB J. 33, 11959‐11972 (2019). http://www.fasebj.org

show abstract

All-trans retinoic acid enhances bystander effect of suicide gene therapy in the treatment of breast cancer

Cited by 25 publications

References 25 publications

Gap junctions and cancer: communicating for 50 years

Gap junctions and cancer: communicating for 50 years

Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling

Contact Info

Product

Resources

About