scholarly journals EMT and Cancer Cell Stemness Associated With Chemotherapeutic Resistance in Esophageal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaojie Liu ◽  
Mingjing He ◽  
Linlin Li ◽  
Xiya Wang ◽  
Shuhua Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Esophageal Cancer Cells ◽  
Resistant Cells

Drug resistance often occurs after chemotherapy in esophageal cancer patients, leading to cancer metastasis and recurrence. However, the relationship among cancer cell migration, recurrence and drug resistance in esophageal cancer drug-resistant cells has not been clearly explained. In this study, we constructed paclitaxel (PTX)-resistant esophageal cancer cells to explore the causes of drug resistance and poor prognosis after chemotherapy in esophageal cancer. Colony formation assay was used to evaluate the difference of colony formation between parental cells and drug resistance cells. Microsphere formation assay was used to examine the phenotype of stem cells. Wound healing and Transwell assays were used to detect the migration ability of drug-resistant cells. Western blotting and immunofluorescence assays were used to explore the mechanisms. Finally, we used nude mouse xenograft model to explore the tumor characteristics and the expression of relative proteins to verify our findings in vivo. Our study demonstrated that the cancer cell stemness characteristics exist in drug-resistant esophageal cancer cells, that expressed the biomarkers of stem cells and were prone to epithelial-mesenchymal transition (EMT). Our results suggested that the expression of EMT biomarkers and stemness-related proteins increased in esophageal cancer cells after continuously using chemotherapeutic drugs for a period of time. This study indicated that simultaneously targeting EMT and stemness could be a better strategy for the treatment of esophageal cancer drug resistance.

scholarly journals Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells

2019 ◽  
Author(s):  
Shifeng Shi ◽  
Xin Huang ◽  
Xiao Ma ◽  
Xiaoyan Zhu ◽  
Qinxian Zhang
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cisplatin Resistance ◽  
High Expression ◽  
Drug Resistant ◽  
Cellular Resistance ◽  
Esophageal Cancer Cells

AbstractPurposeChemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor’s acquired drug resistance, the related action mechanism is still not explored specifically.MethodsTo elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin.ResultsSmall RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-resistant cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine–cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin’s inhibition of the cell cycle of sensitive cells.ConclusionSensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.

Apatinib affects the proliferation, migration and apoptosis of esophageal cancer cells both in vitro and in xenografts by regulating Ras/Raf/MEK/ERK and JAK2/STAT3 signaling pathways.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15501-e15501
Author(s):  
Jingping Yu
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Formation Rate ◽  
Xenograft Model ◽  
Control Group ◽  
Expression Levels ◽  
Esophageal Cancer Cells ◽  
Carcinoma Xenograft

e15501 Background: To investigate the effects of apatinib on esophageal cancer cells in vitro and xenograft models, and discuss the mechanisms of its actions. Methods: Used various assays to measure the different biological processes of esophageal cancer cells: used MTT assay to measure the proliferation rate; used transwell assay to determine the migration capacity and used colony formation assay to assess the clone formation rate. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression levels of VEGF and VEGFR2 were measured by qRT-PCR. The concentration of VEGF in the supernatant of cancer cell was assessed by ELISA. The expression levels of MEK, ERK, p-MEK, p-ERK, STAT3, p-STAT3, CHK2 and CDC2 after VEGF stimulation were detected by western blot. We also established human esophageal squamous carcinoma xenograft model in nude mice. The mice were randomly divided into healthy control group, low dose group (250mg) and high dose group (500mg), with 6 mice in each group. The tumor growth rate of each group was calculated, and the expression levels of VEGF and VEGFR2 in tumor tissues were detected by immunohistochemistry. Results: Apatinib inhibited the proliferation of esophageal cancer cell in a time-dependent (P < 0.05) and concentration-dependent (P < 0.05) manner; it also inhibited the cell migration capacity (P < 0.05) and colony formation rate (P < 0. 05). In addition, apatinib induced apoptosis in esophageal cancer cells and increased the proportion of cells in G2 / M phase (P < 0.05). The mRNA levels of VEGF (P < 0.05) and VEGFR2 (P < 0.05) and the protein levels of VEGF (P < 0.05) were also suppressed by apatinib. Western blot showed that apatinib could down-regulate the expression of p-MEK, p-ERK, STAT3, p-STAT3, CHK2 and CDC2 (P < 0.05). The inhibition rates of apatinib in esophageal carcinoma xenograft model was 29.25% and 19.96% for 250mg and 500mg drug treatment groups. Compared with healthy control group, the VEGF levels in drug treatment groups were not significantly different (P > 0.05), but the VEGFR2 levels were significantly decreased (P < 0.05). Conclusions: Apatinib can induce apoptosis of esophageal cancer cell KYSE-150 and ECA-109, and inhibit the cell proliferation, migration and colony formation. Moreover, apatinib can inhibit the tumor growth in esophageal carcinoma xenograft models. This inhibitory action of apatinib is related to the alterations in VEGF-related pathways such as Ras / Raf / MEK / ERK and JAK2 / STAT3 pathways.

scholarly journals The involvement of MCTP1 in the drug-resistance of esophageal cancer cells

2020 ◽  
Author(s):  
Lingsuo Kong ◽  
Ran Wei ◽  
Wan Yang ◽  
Lanren Chen ◽  
Liting Qian
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Esophageal Cancer ◽  
Effective Treatment ◽  
Cancer Cells ◽  
Cell Lines ◽  
Drug Resistant ◽  
Proliferation And Apoptosis ◽  
Ec Cells ◽  
Esophageal Cancer Cells

Abstract Background: Accumulating studies demonstrated that drug-resistance remains a great obstacle for the effective treatment of cancers. Esophageal cancer (EC) is still one of the most common cancers worldwide, which also suffers from drug-resistance during clinical treatment. Methods: We performed the drug-resistance profiling assays and identified several drug-resistant and drug-sensitive EC cell lines. The following methylation sequencing showed that the MCTP1 gene is hypermethylated in the drug-resistant EC cells. Results: As a result, the expression of MCTP1 is down-regulated in the drug-resistant EC cells. Down-regulation of MCTP1 also affects the cell proliferation and apoptosis of EC cells, as revealed by the cell proliferation and apoptosis assays. Further investigations proposed two signaling pathways that might involve in the MCTP1-mediated drug-resistance of EC cell. Conclusions: All these results suggested that MCTP1 is associated with the drug-resistance of EC cells, which has implications for further design of new biomarker of EC treatment.

scholarly journals TSPAN9 suppresses the chemosensitivity of gastric cancer to 5-fluorouracil by promoting autophagy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yaoyue Qi ◽  
Weiwei Qi ◽  
Shihai Liu ◽  
Libin Sun ◽  
Aiping Ding ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Transmembrane Protein ◽  
Pi3k Pathway ◽  
Drug Resistant ◽  
Gastric Cancer Cells ◽  
Autophagy Pathway ◽  
Resistant Cells

Abstract Background The issue of drug resistance in gastric cancer has attracted global attention. TSPAN9, a 4-transmembrane protein that plays an important role in tumor progression and signal transduction, has been found to be closely related to tumor invasion, metastasis, and autophagy. Methods Immunoblotting was used to evaluate TSPAN9 expression in parental and drug-resistant gastric cancer cells. Functional assays, such as the CCK-8 assay, were used to detect the proliferation of gastric cancer cells and the response of TSPAN9 to 5-fluorouracil (5-FU). Western blotting was used to analyze the expression of constituents of the PI3K/AKT/mTOR-mediated autophagy pathway induced by TSPAN9. Coimmunoprecipitation was performed to assess the specific mechanism by which TSPAN9 affects the PI3K pathway. Results We demonstrated that TSPAN9 is overexpressed in 5-FU-resistant cells compared to parental cells. 5-FU-mediated inhibition of cell proliferation can be significantly restored by increasing TSPAN9 expression, and inhibiting this expression in drug-resistant cells can restore the sensitivity of the cells to 5-FU. In addition, TSPAN9 also significantly promoted autophagy in gastric cancer cells in vitro. Further studies indicated that TSPAN9 downregulates the expression of PI3K and proteins associated with PI3K-mediated autophagy. In addition, TSPAN9 interacts with PI3K and inhibits its catalytic activity. Conclusion The current study reveals the important role of TSPAN9 in drug resistance to 5-FU in gastric cancer. It also provides a new target to clinically address drug-resistant gastric cancer and will contribute to the treatment strategy of this disease.

scholarly journals Bone marrow mesenchymal stem cells-derived exosomal microRNA-193a reduces cisplatin resistance of non-small cell lung cancer cells via targeting LRRC1

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Hongbo Wu ◽  
Xiaoqian Mu ◽  
Lei Liu ◽  
Huijuan Wu ◽  
Xiufeng Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Colony Formation ◽  
Small Cell ◽  
Drug Resistant ◽  
Small Cell Lung ◽  
Marrow Mesenchymal Stem Cells ◽  
Resistant Cells

Abstract Exosomes are small endogenous membrane vesicles that can mediate cell communication by transferring genetic materials. Based on that, exosomes have always been discussed as a cargo carrier for microRNA (miRNA) transportation. Accumulating data have reported the inhibitory effects of microRNA-193a (miR-193a) on non-small cell lung cancer (NSCLC) cell progression. However, the mechanisms of miR-193a delivery to cancer cells and miR-193a in exosomes have not been explored clearly in NSCLC. Given that, this work aims to decode exosomal miR-193a in cisplatin (DDP) resistance of NSCLC cells. A549 and H1299 cell lines were screened out and their parent cells and drug-resistant cells were co-cultured with human bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exo) that had been transfected with miR-193a mimic or si-LRRC1 to detect the colony formation, migration, apoptosis, invasion and proliferation of NSCLC cells. In vivo experiment was conducted to verify the in vitro results. BMSC-Exo with upregulated miR-193a and downregulated LRRC1 suppressed colony formation, invasion, proliferation and migration as well as advanced apoptosis of NSCLC parent cells and drug-resistant cells. BMSC-Exo combined with upregulated miR-193a reduced tumor volume and weight in mice with NSCLC. Functional studies report that BMSC-Exo shuffle miR-193a to suppress the colony formation, invasion, migration, and proliferation as well as advance apoptosis of NSCLC DDP-resistant cells via downregulating LRRC1.

Oncolytic adenovirus expressing apoptotic genes targets radiation resistant (RR) esophageal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21043-21043
Author(s):  
J. Y. Chang ◽  
R. Komaki ◽  
X. Zhang ◽  
L. Wang ◽  
B. Fang
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Radiation Exposure ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Esophageal Cancer Cell ◽  
Esophageal Cancer Cells ◽  
Trans Gene ◽  
Fractionated Radiation

21043 Background: Only 25% of esophageal cancer patients achieve pathological complete response after standard chemoradiotherapy. Radiation dose escalation is associated with higher toxicity but no therapeutic improvement. In addition, esophageal cancer cells may develop radiation resistance (RR) after fractionated radiation exposure. Therefore, molecular targeting therapy for RR esophageal cancer is urgently needed. Methods: Six pairs of RR esophageal cancer cell lines were established by applying continuous 2 Gy fractionated irradiation. Ad/TRAIL-E1, an oncolytic adenoviral vector expressing both apoptotic TRAIL and viral E1A genes under the control of tumor specific human telomerase reverse transcriptase promoter, was constructed. Phosphate buffer solution and vectors expressing the TRAIL gene only, the GFP marker protein only, or the E1A gene only served as controls. Trans-gene expression, apoptosis activation, and the RR esophageal cancer cells targeted were evaluated in vitro and in vivo. A human esophageal RR cancer model was established and locally treated with Ad/TRAIL-E1 or controls. Results: After fractionated radiation exposure, esophageal cancer cell lines developed RR (up to 25-fold) that was associated with activation of the anti-apoptotic pathway. Ad/TRAIL-E1 activated an apoptotic cascade of caspases and selectively killed esophageal cancer cells but not normal cells. Ad/TRAIL-E1 preferentially targeted RR stem-like cancer cells with higher trans-gene expression and cell killing compared with parental cells. Overexpression (3 times) of Coxsackie's and adenoviral receptors in RR esophageal cancer cells compared with parental cells was noted. Ad/TRAIL-E1 therapy resulted in 40% tumor-free survival without the treatment- related toxicity found in human RR esophageal adenocarcinoma mouse models (p<0.05 as compared with controls). Conclusions: Esophageal cancer cells develop RR after fractionated radiation exposure. Ad/TRAIL-E1 preferentially targeted RR stem-like esophageal cancer cells, which resulted in a 40% cure rate. No significant financial relationships to disclose.

scholarly journals Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 483 ◽  
Author(s):  
Meghan Leary ◽  
Sarah Heerboth ◽  
Karolina Lapinska ◽  
Sibaji Sarkar
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Progenitor Cells ◽  
Rational Design ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Combination Therapies ◽  
Cancer Drug Resistance ◽  
Rational Development

Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherapy, and to prevent formation of drug resistant cancer cells. It is also necessary to prevent the formation of cancer progenitor cells by epigenetic mechanisms, as cancer progenitor cells are insensitive to standard therapies. In this article, we emphasize the role for the rational development of combination therapy, including epigenetic drugs, in achieving these goals.

scholarly journals Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer

2017 ◽  
Vol 43 (3) ◽  
pp. 1126-1139 ◽  
Author(s):  
Xiang Yang ◽  
Fan Bai ◽  
Yichen Xu ◽  
Yitian Chen ◽  
Longbang Chen
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Colony Formation ◽  
Small Cell ◽  
Beclin 1 ◽  
Drug Resistant ◽  
Small Cell Lung ◽  
Resistant Cells

Background/Aims: Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells. Methods: We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP) -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients’ chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor. Results: Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells. Conclusion: Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.

Sign in / Sign up

Export Citation Format

Share Document