Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer

Abstract Pancreatic cancer is the fourth leading cause of death worldwide due to its poorest prognoses with a 7% 5-year survival rate. Eighty percent of pancreatic cancer patients relapse after chemotherapy and develop early metastasis and drug resistance. Resistance to nucleoside analog gemcitabine frequently used in first-line therapy is an urgent issue in pancreatic cancer treatment. Expression of mucin (MUC) glycoproteins has been shown to enhance chemoresistance via increased cell stemness. Here we show interlukine-17 receptor B (IL-17RB) expression is positively correlated with MUC1 and MUC4 expression in pancreatic cancer cells and tumor tissue. Moreover, IL-17RB transcriptionally up-regulates expression of MUC1 and MUC4 to enhance cancer stem-like properties and resistance to gemcitabine. These results suggest IL-17RB can be a potential target for pancreatic cancer therapy. Indeed, treatment with IL-17RB-neutralizing antibody has a synergistic effect in combination with gemcitabine for killing pancreatic cancer cells. Altogether, these findings provide feasible applications for IL-17RB-targeting therapy in pancreatic cancer treatment.

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The rational design of a gemcitabine prodrug with AIE-based intracellular light-up characteristics for selective suppression of pancreatic cancer cells

Chemical Communications ◽

10.1039/c5cc06654a ◽

2015 ◽

Vol 51 (98) ◽

pp. 17435-17438 ◽

Cited By ~ 38

Author(s):

Haijie Han ◽

Qiao Jin ◽

Yin Wang ◽

Yangjun Chen ◽

Jian Ji

Keyword(s):

Pancreatic Cancer ◽

Cancer Therapy ◽

Cancer Cells ◽

Rational Design ◽

Image Guided ◽

Pancreatic Cancer Cells ◽

Selective Suppression ◽

Pancreatic Cancer Therapy

An enzyme and reduction-activatable gemcitabine prodrug with AIE properties was designed for targeted and image-guided pancreatic cancer therapy.

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Resveratrol-Induced Downregulation of NAF-1 Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine via the ROS/Nrf2 Signaling Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/9482018 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16 ◽

Cited By ~ 14

Author(s):

Liang Cheng ◽

Bin Yan ◽

Ke Chen ◽

Zhengdong Jiang ◽

Cancan Zhou ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Anticancer Agent ◽

Oxygen Species ◽

Pancreatic Cancer Cells ◽

Ros Accumulation ◽

Cellular Reactive Oxygen Species ◽

Pancreatic Cancer Therapy ◽

Mitochondrial Membrane Protein

NAF-1 (nutrient-deprivation autophagy factor-1), which is an outer mitochondrial membrane protein, is known to play important roles in calcium metabolism, antiapoptosis, and antiautophagy. Resveratrol, a natural polyphenolic compound, is considered as a potent anticancer agent. Nevertheless, the molecular mechanisms underlying the effects of resveratrol and NAF-1 and their mediation of drug resistance in pancreatic cancer remain unclear. Here, we demonstrate that resveratrol suppresses the expression of NAF-1 in pancreatic cancer cells by inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling. In addition, the knockdown of NAF-1 activates apoptosis and impedes the proliferation of pancreatic cancer cells. More importantly, the targeting of NAF-1 by resveratrol can improve the sensitivity of pancreatic cancer cells to gemcitabine. These results highlight the significance of strategies that target NAF-1, which may enhance the efficacy of gemcitabine in pancreatic cancer therapy.

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Dihydroartemisinin induces apoptosis and downregulates glucose metabolism in JF-305 pancreatic cancer cells

RSC Advances ◽

10.1039/c8ra00565f ◽

2018 ◽

Vol 8 (37) ◽

pp. 20692-20700

Author(s):

Wenhe Zhu ◽

Wei Zhang ◽

Na Xu ◽

Yawei Li ◽

Junjie Xu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Glucose Metabolism ◽

Cancer Treatment ◽

Cancer Cells ◽

Cancer Cell ◽

Therapeutic Target ◽

Pancreatic Cancer Cells ◽

Promising Therapeutic Target

Cancer cell promotion of glycolysis provides a promising therapeutic target for cancer treatment.

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Mitofusin2 Induces Cell Autophagy of Pancreatic Cancer through Inhibiting the PI3K/Akt/mTOR Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2798070 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Ran Xue ◽

Qinghua Meng ◽

Di Lu ◽

Xinjuan Liu ◽

Yanbin Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Treatment ◽

Cancer Cells ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Mtor Signaling ◽

Biological Functions ◽

Mtor Signaling Pathway ◽

Pancreatic Cancer Cells

Aim. Pancreatic cancer is one of the most quickly fatal cancers around the world. Burgeoning researches have begun to prove that mitochondria play a crucial role in cancer treatment. Mitofusin2 (Mfn2) plays an indispensable role in mitochondrial fusion and adjusting function. However, the role and underlying mechanisms of Mfn2 on cell autophagy of pancreatic cancer is still unclear. Our aim was to explore the effect of Mfn2 on multiple biological functions involving cell autophagy in pancreatic cancer. Methods. Pancreatic cancer cell line, Aspc-1, was treated with Ad-Mfn2 overexpression. Western blotting, caspase-3 activity measurement, and CCK-8 and reactive oxygen species (ROS) assay were used to examine the effects of Mfn2 on pancreatic cancer autophagy, apoptosis, cell proliferation, oxidative stress, and PI3K/Akt/mTOR signaling. The expression of tissue Mfn2 was detected by immunohistochemical staining. Survival analysis of Mfn2 was evaluated by OncoLnc. Results. Mfn2 improved the expression of LC3-II and Bax and downregulated the expression of P62 and Bcl-2 in pancreatic cancer cells. Meanwhile, Mfn2 also significantly inhibited the expression of p-PI3K, p-Akt, and p-mTOR proteins in pancreatic cancer cells. In addition, Mfn2 inhibited pancreatic cancer cell proliferation and ROS production. Assessment of Kaplan-Meier curves showed that Mfn2− pancreatic cancer has a worse prognosis than Mfn2+ pancreatic cancer has. Conclusions. Our finding suggests that Mfn2 induces cell autophagy of pancreatic cancer through inhibiting the PI3K/Akt/mTOR signaling pathway. Meanwhile, Mfn2 also influences multiple biological functions of pancreatic cancer cells. Mfn2 may act as a therapeutic target in pancreatic cancer treatment.

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