Synergistic antitumor effects of radiation and proteasome inhibitor treatment in pancreatic cancer through the induction of autophagy and the downregulation of TRAF6

Chiu, Hung-Wen; Lin, Shu; Lin, Li; Hsu, Yung Ho; Lin, Yuh Feng; Ho, Sheng Yow; Wu, Yuan; Wang, Ying Jan

doi:10.1016/j.canlet.2015.05.025

Cited by 40 publications

(29 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results were cross validated by adding the autophagy inhibitor 3-methyladenine (3-MA). The experiment was also repeated with an animal model and it was found that the combined treatment was able to increase tumour growth delay when compared with the MG132 or radiotherapy alone group [32]. This study also showed the down-regulation of TRAF6 though the combination of MG132 and irradiation.…”

Section: Effect Of Autophagy Modulation On Radiotherapy Efficacy In Dmentioning

confidence: 73%

“…Chiu et al (2015) [32] investigated the action of a proteasome inhibitor MG132 and radiotherapy in two pancreatic cancer cell lines MIA PaCa-2 and PANC-1 in vitro and in vivo. Results showed that the combined modalities increased ER stress, increased IRE1α protein level, promoted autophagy induction, increased detection of early apoptosis and cell death and increased MAP1LC3 level.…”

Section: Effect Of Autophagy Modulation On Radiotherapy Efficacy In Dmentioning

confidence: 99%

See 1 more Smart Citation

Influence of autophagy on the efficacy of radiotherapy

Tam

Law

2017

Radiat Oncol

View full text Add to dashboard Cite

Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly, autophagy could play both pro-death and pro-survival roles in influencing the development of cancer via various signal pathways. As radiotherapy is one of the main treatment modalities for cancer, we reviewed the effect of autophagy modulations on radiosensitivity and radiotherapy efficacy in various cancer types. The future development of autophagy modifications for improving radiotherapy efficacy and cancer prognosis will also be discussed.

show abstract

Section: Effect Of Autophagy Modulation On Radiotherapy Efficacy In Dmentioning

confidence: 73%

Section: Effect Of Autophagy Modulation On Radiotherapy Efficacy In Dmentioning

confidence: 99%

Influence of autophagy on the efficacy of radiotherapy

Tam

Law

2017

Radiat Oncol

View full text Add to dashboard Cite

show abstract

“…KB-R7943 may therefore cause cancer cell death by permeabilizing the ER membrane. In addition, apoptosis is closely related to ER stress during chemotherapy [35]. Here, the autophagy inhibitor CQ enhanced the apoptosis-inducing effect of KB-R7943 treatment in prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux

et al. 2016

View full text Add to dashboard Cite

We explored the effects of KB-R7943, an inhibitor of reverse-mode NCX1 activity, in prostate cancer (PCa). NCX1 was overexpressed in PCa tissues and cell lines, and higher NCX1 levels were associated higher PCa grades. At concentrations greater than 10 μM, KB-R7943 dose-dependently decreased PC3 and LNCaP cell viability. KB-R7943 also increased cell cycle G1/S phase arrest and induced apoptosis in PC3 cells. KB-R7943 increased autophagosome accumulation in PCa cells as indicated by increases in LC3-II levels and eGFP-LC3 puncta. Combined treatment with chloroquine (CQ) and KB-R7943 decreased P62 and increased LC3-II protein levels in PC3 cells, indicating that KB-R7943 blocked autophagic flux. KB-R7943 induced autophagosome accumulation mainly by downregulating the PI3K/AKT/m-TOR pathway and upregulating the JNK pathway. In xenograft experiments, KB-R7943 inhibited tumor growth. Combined treatment with KB-R7943 and an autophagy inhibitor inhibited growth and increased apoptosis. These results indicate that KB-R7943 promotes cell death in PCa by activating the JNK signaling pathway and blocking autophagic flux.

show abstract

“…A recent study has indicated that TRAF6 is recruited to the phosphorylated discoidin neuropilin-like membrane protein DCBLD2 Y750, subsequently increasing its E3 ubiquitin ligase activity and then activating Akt, which promotes EGFR-driven glioma and head and neck cancers [103]. Furthermore, pancreatic cancer that exhibits slower growth can result from TRAF6 inhibition in vivo and in vitro [104]. The roles of the other members of the TRAF family in carcinogenesis are still unclear.…”

Section: Tlr Signaling In Cancermentioning

confidence: 97%