Antiproliferative and Overadditive Effects of Rapamycin and FTY720 in Pancreatic Cancer Cells In Vitro

Shen, Yan; Wang, X.; Xia, Weiliang; Wang, C.; Cai, M; Xie, Haiyang; Zheng, Shusen

doi:10.1016/j.transproceed.2008.03.150

Cited by 18 publications

(11 citation statements)

References 12 publications

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“…In vitro , Rapa combined with inhibition of the Notch pathway showed a greater efficacy in the treatment of patients with pancreas cancer [21]. Rapa showed dose-dependent antiproliferative effects on pancreatic carcinoma cell lines in vitro both alone and in combination with FTY720 [22]. …”

Section: Resultsmentioning

confidence: 99%

Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy

Dai

Gao

et al. 2012

IJMS

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Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells.

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Section: Resultsmentioning

confidence: 99%

Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy

Dai

Gao

et al. 2012

IJMS

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“…Hence, as a sphingosine analog, fingolimod has been studied in in vitro and in vivo for its potential anticancer effects. Indeed, fingolimod has been shown in preclinical studies to have anticancer activity in various cancer cell types, including bladder cancer 87, breast cancers (88)(89)(90)(91), glioblastoma (92,93), hepatocellular carcinoma (94)(95)(96), malignant mesothelioma (97), leukemia and lymphoma (98)(99)(100)(101)(102)(103)(104), lung cancer (105)(106)(107), liver cancer (108), pancreatic cancer (109), bladder cancer (87), renal cancer (110); glioma (111), gastrointestinal cancer (112), and ovarian cancer (113). Fingolimod has also been shown to be an important therapy sensitizer in several studies.…”

Section: Sphingosine 1-p Receptor (S1pr) Receptormentioning

confidence: 99%

Multiple Sclerosis and Cancer: The Ying-Yang Effect of Disease Modifying Therapies

Melamed

Lee

2020

Front. Immunol.

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Over the past two decades, the field of multiple sclerosis (MS) has been transformed by the rapidly expanding arsenal of new disease modifying therapies (DMTs). Current DMTs for MS aim to modulate innate and adaptive immune responses toward a less inflammatory phenotype. Since the immune system is also critical for identifying and eliminating malignant cells, immunosuppression from DMTs may predictably increase the risk of cancer development in MS patients. Compared with healthy controls, patients with autoimmune conditions, such as MS, may already have a higher risk of developing certain malignancies and this risk may further be magnified by DMT treatments. For those patients who develop both MS and cancer, these comorbid presentations create a challenge for clinicians on how to therapeutically address management of cancer in the context of MS autoimmunity. As there are currently no accepted guidelines for managing MS patients with prior history of or newly developed malignancy, we undertook this review to evaluate the molecular mechanisms of current DMTs and their potential for instigating and treating cancer in patients living with MS.

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“…In addition, modulators of sphingosine-1-phosphate signaling are being tested as potential therapeutics for patients with cancer. Drugs such as fingolimod were proven to inhibit cancer growth and its invasiveness [61,62]. Importantly, this drug is already being used for the treatment of patients with multiple sclerosis and, according to clinical results, is tolerated relatively well by patients and has quite limited side effects [63].…”

Section: Bone Marrow-pancreatic Cancer Axismentioning

confidence: 99%

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

Błogowski

Bodnarczuk²,

Starzyńska

2016

Stem Cells Translational Medicine

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Pancreatic adenocarcinoma remains one of the most challenging diseases of modern gastroenterology, and, even though considerable effort has been put into understanding its pathogenesis, the exact molecular mechanisms underlying the development and/or systemic progression of this malignancy still remain unclear. Recently, much attention has been paid to the potential role of bone marrowderived stem cells (BMSCs) in this malignancy. Hence, herein, we comprehensively review the most recent discoveries and current achievements and concepts in this field. Specifically, we discuss the significance of identifying pancreatic cancer stem cells and novel therapeutic approaches involving molecular interference of their metabolism. We also describe advances in the current understanding of the biochemical and molecular mechanisms responsible for BMSC mobilization during pancreatic cancer development and systemic spread. Finally, we summarize experimental, translational, and/or clinical evidence regarding the contribution of bone marrow-derived mesenchymal stem cells, endothelial progenitor cells, hematopoietic stem/progenitor cells, and pancreatic stellate cells in pancreatic cancer development/progression. We also present their potential therapeutic value for the treatment of this deadly malignancy in humans. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:938-945 SIGNIFICANCE Different bone marrow-derived stem cell populations contribute to the development and/or progression of pancreatic cancer, and they might also be a promising "weapon" that can be used for anticancer treatments in humans. Even though the exact role of these stem cells in pancreatic cancer development and/or progression in humans still remains unclear, this concept continues to drive a completely novel scientific avenue in pancreatic cancer research and gives rise to innovative ideas regarding novel therapeutic modalities that can be safely offered to patients.

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Antiproliferative and Overadditive Effects of Rapamycin and FTY720 in Pancreatic Cancer Cells In Vitro

Cited by 18 publications

References 12 publications

Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy

Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy

Multiple Sclerosis and Cancer: The Ying-Yang Effect of Disease Modifying Therapies

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

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