Interplay Between Gemcitabine and Erlotinib Over Pancreatic Adenocarcinoma Cells

Torres, Carolina; Linares, Ana María; Alejandre, M.J.; Palomino-Morales, Rogelio; Delgado, Juan Ramón; Perales, Sonia

doi:10.1097/mpa.0000000000000452

Cited by 7 publications

(6 citation statements)

References 52 publications

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“…Previous studies demonstrated that GEM inhibits the expression of cyclin D and Bcl-2, inducing G1 phase arrest in many types of human cancer cells including NSCLC. 27-29 Our results are consistent with these reports. The levels of cyclin D1 and Bcl-2 proteins were decreased in cells treated with GEM alone.…”

Section: Resultssupporting

confidence: 94%

Metuzumab enhanced chemosensitivity and apoptosis in non-small cell lung carcinoma

Fěng

Wang

Sun

et al. 2017

Cancer Biology & Therapy

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Targeted therapeutics is used as an alternative treatment of non-small cell lung cancer (NSCLC); however, treatment effect is far from being satisfactory, and therefore identification of new targets is needed. We have previously shown that metuzumab inhibit tumor growth in vivo. The present study was performed to investigate the anti-tumor efficacy of metuzumab combined with gemcitabine and cisplatin (GP), paclitaxel and cisplatin (TP) or navelbine and cisplatin (NP) regimens in multiple NSCLC cell lines. Our results demonstrate that, in comparison to single agent metuzumab or GP treated cells, metuzumab combined with GP display inhibitory effects on tumor growth. Furthermore, we found that metuzumab elevated the sensitivity of cell lines to gemcitabine, which was identified by MTT assay. Flow cytometric analysis showed that metuzumab combined with gemcitabine (GEM) treatment led to an obvious G1 arrest and an elevated apoptosis in A549, NCI-H460 and NCI-H520 cells. Western blot analysis also demonstrated a significantly reduced level of cyclin D1, Bcl-2, and an obviously increase level of Bax and full-length caspase-3 in A549, NCI-H460 and NCI-H520 cells treated with metuzumab/gemcitabine combination in comparison with single agent treated cells. In addition, metuzumab/gemcitabine treated A549, NCI-H460 and NCI-H520 cells also demonstrated a significantly increase in deoxycytidine kinase (dCK) protein level compared with single agent metuzumab or gemcitabine treated cells. Xenograft models also demonstrated that this metuzumab/gemcitabine combination led to upregulation of dCK. Taken together, the mechanisms of metuzumab combined with GP repress tumor growth were that the combined treatment significantly inhibited the tumor cell proliferation, apoptosis and cell cycle in vitro and in vivo and at least partially by induction of dCK expression. Our results suggested that metuzumab could significantly enhance chemosensitivity of human NSCLC cells to gemcitabine. Metuzumab/gemcitabine combination treatment may be a potentially useful therapeutic regimen for NSCLC patients.

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Section: Resultssupporting

confidence: 94%

Metuzumab enhanced chemosensitivity and apoptosis in non-small cell lung carcinoma

Fěng

Wang

Sun

et al. 2017

Cancer Biology & Therapy

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“…Blockchain extension also exerts its anti‐tumor activity through a series of other cellular mechanisms on DNA synthesis. 18 , 19 Anlotinib is a multi‐target drug; however, the purpose of this study was to investigate the anti‐tumor mechanism of anlotinib combined with gemcitabine. To determine whether the inhibitory effect of anlotinib combined with gemcitabine on cell growth inhibition was due to cell cycle arrest, we analyzed the cell cycle distribution of these cells using FCM with PI/RNase staining.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that gemcitabine can cause S phase cell cycle arrest, and under certain conditions, it prevents the G1 phase transition to S phase. Blockchain extension also exerts its anti‐tumor activity through a series of other cellular mechanisms on DNA synthesis 18,19 . Anlotinib is a multi‐target drug; however, the purpose of this study was to investigate the anti‐tumor mechanism of anlotinib combined with gemcitabine.…”

Section: Resultsmentioning

confidence: 99%

Combination of anlotinib and gemcitabine promotes the G0/G1 cell cycle arrest and apoptosis of intrahepatic cholangiocarcinoma in vitro

Fan

Liu

et al. 2021

Clinical Laboratory Analysis

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“…For example, a recent report suggested that median progression-free survival (PFS) and overall survival (OS) were improved with Nab-paclitaxel plus gemcitabine treatment in both locally advanced and metastasized PDAC, but hematologic toxicity was observed and dose reductions were performed in most of the patients [13,14]. Erlotinib, which acts as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and blocks its downstream signaling cascade to modulate cancer proliferation, differentiation, apoptosis, invasion, and metastasis, has been shown to increase the efficacy of gemcitabine towards radiation or recurrent PDAC tumor growth in mice [46][47][48][49][50]. Despite modest survival benefits observed from gemcitabine and erlotinib in clinical studies, combination treatment of gemcitabine and erlotinib was also approved for use in the advanced disease of PDAC, which prolongs 1-year survival by only 23% [17].…”

Section: Discussionmentioning

confidence: 99%

Targeted Dual Intervention-Oriented Drug-Encapsulated (DIODE) Nanoformulations for Improved Treatment of Pancreatic Cancer

Madamsetty

Pal

Dutta

et al. 2020

Cancers

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Despite recent advancements, effective treatment for pancreatic ductal adenocarcinoma (PDAC) has remained elusive. The overall survival rate in PDAC patients has been dismally low due to resistance to standard therapies. In fact, the failure of monotherapies to provide long-term survival benefits in patients led to ascension of several combination therapies for PDAC treatment. However, these combination therapies provided modest survival improvements while increasing treatment-related adverse side effects. Hence, recent developments in drug delivery methods hold the potential for enhancing therapeutic benefits by offering cocktail drug loading and minimizing chemotherapy-associated side effects. Nanoformulations-aided deliveries of anticancer agents have been a success in recent years. Yet, improving the tumor-targeted delivery of drugs to PDAC remains a major hurdle. In the present paper, we developed several new tumor-targeted dual intervention-oriented drug-encapsulated (DIODE) liposomes. We successfully formulated liposomes loaded with gemcitabine (G), paclitaxel (P), erlotinib (E), XL-184 (c-Met inhibitor, X), and their combinations (GP, GE, and GX) and evaluated their in vitro and in vivo efficacies. Our novel DIODE liposomal formulations improved median survival in comparison with gemcitabine-loaded liposomes or vehicle. Our findings are suggestive of the importance of the targeted delivery for combination therapies in improving pancreatic cancer treatment.

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Interplay Between Gemcitabine and Erlotinib Over Pancreatic Adenocarcinoma Cells

Abstract: Our data suggest that, although gemcitabine and erlotinib exert antiproliferative effects over pancreatic cancer cell lines, the gemcitabine-induced activation of NF-κB expression and its DNA-binding activities are important drawbacks of this treatment against pancreatic cancer.

Cited by 7 publications

References 52 publications

Metuzumab enhanced chemosensitivity and apoptosis in non-small cell lung carcinoma

Metuzumab enhanced chemosensitivity and apoptosis in non-small cell lung carcinoma

Combination of anlotinib and gemcitabine promotes the G0/G1 cell cycle arrest and apoptosis of intrahepatic cholangiocarcinoma in vitro

Targeted Dual Intervention-Oriented Drug-Encapsulated (DIODE) Nanoformulations for Improved Treatment of Pancreatic Cancer

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