Antitumor Effects of Eribulin Mesylate in Gemcitabine-resistant Pancreatic Cancer Cell Lines

Abstract

Abstract. Background respectively), but had no effect on hPE cells. Microscopic examination of Pancreatic cancer is a commonly diagnosed cancer worldwide, with an extremely poor prognosis, and is the fourth leading cause of cancer-related deaths (1). In patients with recurrent, metastatic, or advanced pancreatic cancer, chemotherapy can prolong survival and improve quality of life compared with best supportive care (2, 3). In recent years, gemcitabine, a novel pyrimidine nucleoside analog, has become the standard chemotherapeutic agent used in patients with pancreatic cancer (3). Despite considerable efforts to improve outcomes for these patients, response rates to chemotherapy remain low and the median survival of patients with advanced disease remains in the range of 6 to 10 months (3, 4). Therefore, more effective drugs or combination therapies for pancreatic cancer are needed. and human pancreatic endoderm (hPE) cells were used to evaluate the antitumor effects of gemcitabine and eribulin mesylate. Cell viability after treatment of cells with different concentrations of gemcitabine and eribulin mesylate was evaluated using water-soluble tetrazolium salts (WST) assays; cytotoxic effects were evaluated on the basis of morphological changes to cells. Results: Gemcitabine had no effect on cell viability of AsPC-1 nor Panc-1 cells, whereas gemcitabine reduced cell viability of SUIT-2 cells in a dose-dependent manner. Eribulin mesylate significantly reduced cell viability of bothEribulin mesylate, a completely synthetic macrocyclic ketone analog of halichondrin B, which is a natural large polyether macrolide from a rare marine Japanese sponge, acts as a tubulin-binding agent, interfering with microtubule dynamics and suppressing microtubule polymerization without affecting depolymerization (5, 6). Although eribulin mesylate is a novel drug that has shown significant activity and efficacy in heavily pretreated patients with refractory breast cancer, its efficacy in the treatment of pancreatic cancer in patients with a poor prognosis is not clear (7). In the present study, we investigated the antiproliferative effects of eribulin mesylate in three different pancreatic cancer cell lines. Materials and MethodsMaterials and reagents. The present study was performed on three human pancreatic cancer cell lines (AsPC-1, Panc-1, and SUIT-2) and human pancreatic endoderm (hPE) cells. The AsPC-1 and Panc-1 cell lines were purchased from the European Collection of Authenticated Cell Cultures (Salisbury, Wiltshire, UK), the SUIT-2 cell line was purchased from the Japan Health Sciences Foundation (Tokyo, Japan), and the hPE cell line was purchased from Cell Systems Corporation (Kirkland, WA, USA). Dulbecco's modified Eagle's medium (DMEM) and antibiotics (penicillin, streptomycin) were purchased from Invitrogen Corporation (New York, NY, USA). Co. Ltd, Tokyo, Japan) and gemcitabine (Gemzar powder; Eli Lilly Co. Ltd, Tokyo, Japan) were created by diluting the drugs in water to a concentration of 0.5 μg/μl; stock solutions...

Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect?

“…This mechanism involves the suppression of microtubule dynamics and EMT, which can prompt changes in cell morphology [ 33 ]. These changes have also been observed in other cellular models, and particularly in LPS and LMS cell lines, it has been related to cellular differentiation [ 34 , 35 ]. Effects on apoptosis and cell cycle have been also reported, and associated to apoptosis and mitotic arrest in osteosarcoma and breast cell lines [ 36 , 37 ].…”

Chemosensitization and inhibition of pancreatic cancer stem cell proliferation by overexpression of microRNA-205

“…For instance, zidovudine sensitizes GEM-resistant pancreatic cancer cells through Akt/GSK3β-Snail pathway [4]. Similar effects have also been shown by eribulin mesylate and the combination of cotylenin A and phenethyl isothiocyanate in killing GEM-resistant pancreatic cancer cells [5,6]. Although the combination of GEM with nab-paclitaxel [7] and the chemotherapy regimen FOLFIRINOX has shown the overall survival of metastatic PDAC patients; a significant rate of grade 3/4 toxicity was observed [8].…”

Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: Could the combination with other drugs improve its antitumoral effect?

“…This mechanism involves the suppression of microtubule dynamics and EMT, which can prompt changes in cell morphology [33]. These changes have also been observed in other cellular models, and particularly in LPS and LMS cell lines, it has been related to cellular differentiation [34,35].…”