Nanotechnology for delivery of gemcitabine to treat pancreatic cancer

Birhanu, Gebremariam; Javar, Hamid Akbari; Seyedjafari, Ehsan; Zandi-Karimi, Ali

doi:10.1016/j.biopha.2017.01.071

Cited by 53 publications

(27 citation statements)

References 97 publications

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“… 6 , 7 To enhance the cellular uptake of gemcitabine, drug delivery systems, including nanoparticle, liposomes, albumin, and chitosan, have been broadly investigated. 8 …”

Section: Introductionmentioning

confidence: 99%

Gemcitabine-Incorporated G-Quadruplex Aptamer for Targeted Drug Delivery into Pancreas Cancer

Park

Cho

Chae

et al. 2018

Molecular Therapy - Nucleic Acids

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Gemcitabine has been considered a first-line chemotherapy agent for the treatment of pancreatic cancer. However, the initial response rate of gemcitabine is low and chemoresistance occurs frequently. Aptamers can be effectively internalized into cancer cells via binding to target molecules with high affinity and specificity. In the current study, we constructed an aptamer-based gemcitabine delivery system, APTA-12, and assessed its therapeutic effects on pancreatic cancer cells in vitro and in vivo. APTA-12 was effective in vitro and in vivo in pancreatic cancer cells with high expression of nucleolin. The results of in vitro cytotoxicity assays indicated that APTA-12 inhibited the growth of pancreatic cancer cell lines. In vivo evaluation showed that APTA-12 effectively inhibited the growth of pancreatic cancer in Capan-1 tumor-bearing mice compared to mice that received gemcitabine alone or vehicle. These results suggest that the gemcitabine-incorporated APTA-12 aptamer may be a promising targeted therapeutic strategy for pancreatic cancer.

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“… 6 , 7 To enhance the cellular uptake of gemcitabine, drug delivery systems, including nanoparticle, liposomes, albumin, and chitosan, have been broadly investigated. 8 …”

Section: Introductionmentioning

confidence: 99%

Gemcitabine-Incorporated G-Quadruplex Aptamer for Targeted Drug Delivery into Pancreas Cancer

Park

Cho

Chae

et al. 2018

Molecular Therapy - Nucleic Acids

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“…Accompanied with nearly 100% of 5-year mortality rate, pancreatic cancer is one of the most quickly fatal cancers around the world [ 1 ]. Although in recent year we have some amazing improvements in the development of surgery, radiation therapy, and chemotherapy, pancreatic cancer still has a desperate prognosis, mainly because of its aggressive biological behavior and late breaking out of symptoms for clinical diagnosis [ 2 ]. Traits like that bring a mass of difficulties for therapeutic interventions of pancreatic cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

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

Xue

Meng

Lü

et al. 2018

Oxidative Medicine and Cellular Longevity

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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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“…Although a significant increase in the response rate was observed, there was no improvement in survival time with the combination treatment [27]. Therefore, development of an alternative gemcitabine delivery system that increases its availability at tumor sites and maximizes its therapeutic efficacy while minimizing systemic side effects is ongoing [28,29]. Moon et al found that controlled release of gemcitabine from polyamide/polytetrafluoroethylene (PA/PTFE)-covered DESs increases the usefulness of DESs for the treatment of malignant gastrointestinal cancer and cancer-related stenosis [30].…”

Section: Discussionmentioning

confidence: 99%

Local Delivery of Gemcitabine Inhibits Pancreatic and Cholangiocarcinoma Tumor Growth by Promoting Epidermal Growth Factor Receptor Degradation

Jang

Fang

Baek

et al. 2020

IJMS

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Gemcitabine is clinically used to treat certain types of cancers, including pancreatic and biliary cancer. We investigated the signal transduction pathways underlying the local antitumor effects of gemcitabine-eluting membranes (GEMs) implanted in pancreatic/biliary tumor-bearing nude mice. Here, we report that GEMs increased the E3 ubiquitin ligase c-CBL protein level, leading to degradation of epidermal growth factor receptor (EGFR) in SCK and PANC-1 cells. GEMs decreased the RAS and PI3K protein levels, leading to a reduction in the protein levels of active forms of downstream signaling molecules, including PDK, AKT, and GSK3β. GEM reduced proliferation of cancer cells by upregulating cell cycle arrest proteins, particularly p53 and p21, and downregulating cyclin D1 and cyclin B. Moreover, GEMs reduced the levels of proangiogenic factors, including VEGF, VEGFR2, CD31, and HIF-1α, and inhibited tumor cell migration and invasion by inducing the expression of E-cadherin and reducing that of N-cadherin, snail, and vimentin. We demonstrated that local delivery of gemcitabine using GEM implants inhibited tumor cell growth by promoting c-CBL-mediated degradation of EGFR and inhibiting the proliferation, angiogenesis, and epithelial–mesenchymal transition of pancreatic/biliary tumors. Use of gemcitabine-eluting stents can improve stent patency by inhibiting the ingrowth of malignant biliary obstructions.

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Nanotechnology for delivery of gemcitabine to treat pancreatic cancer

Cited by 53 publications

References 97 publications

Gemcitabine-Incorporated G-Quadruplex Aptamer for Targeted Drug Delivery into Pancreas Cancer

Gemcitabine-Incorporated G-Quadruplex Aptamer for Targeted Drug Delivery into Pancreas Cancer

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

Local Delivery of Gemcitabine Inhibits Pancreatic and Cholangiocarcinoma Tumor Growth by Promoting Epidermal Growth Factor Receptor Degradation

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