scholarly journals Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Meng Yang ◽  
Qingqiong Luo ◽  
Xu Chen ◽  
Fuxiang Chen
Keyword(s):  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cancer Treatment ◽  
Cell Carcinoma ◽  
Extracellular Vesicles ◽  
Squamous Cell ◽  
Therapeutic Efficacy ◽  
Bitter Melon ◽  
Anti Inflammatory

Abstract Background Plant-derived extracellular vesicles (PDEVs) have been exploited for cancer treatment with several benefits. Bitter melon is cultivated as a vegetable and folk medicine with anticancer and anti-inflammatory activities. 5-Fluorouracil (5-FU) is widely used for cancer treatment. However, 5-FU-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammation activation induced the resistance of oral squamous cell carcinoma (OSCC) cells to 5-FU. In this study, we explored the potential of bitter melon-derived extracellular vesicles (BMEVs) for enhancing the therapeutic efficacy and reduce the resistance of OSCC to 5-FU. Results Herein, we demonstrate that bitter melon derived extracellular vesicles (BMEVs), in addition to their antitumor activity against OSCC have intrinsic anti-inflammatory functions. BMEVs induced S phase cell cycle arrest and apoptosis. Apoptosis induction was dependent on reactive oxygen species (ROS) production and JUN protein upregulation, since pretreatment with N-acetyl cysteine or catechin hydrate could prevent apoptosis and JUN accumulation, respectively. Surprisingly, BMEVs significantly downregulated NLRP3 expression, although ROS plays a central role in NLRP3 activation. We further assessed the underlying molecular mechanism and proposed that the RNAs of BMEVs, at least in part, mediate anti-inflammatory bioactivity. In our previous studies, NLRP3 activation contributed to the resistance of OSCC cells to 5-FU. Our data clearly indicate that BMEVs could exert a remarkable synergistic therapeutic effect of 5-FU against OSCC both in vitro and in vivo. Most notably, NLRP3 downregulation reduced the resistance of OSCC to 5-FU. Conclusions Together, our findings demonstrate a novel approach to enhance the therapeutic efficacy and reduce the drug resistance of cancer cells to chemotherapeutic agents, which provides proof-of-concept evidence for the future development of PDEVs-enhanced therapy. Graphic Abstract

scholarly journals Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1166 ◽  
Author(s):  
Xin-Hui Khoo ◽  
Ian C. Paterson ◽  
Bey-Hing Goh ◽  
Wai-Leng Lee
Keyword(s):  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Extracellular Vesicles ◽  
Squamous Cell ◽  
Metal Ion ◽  
De Novo ◽  
Protein Profile ◽  
Severe Problem

Drug resistance remains a severe problem in most chemotherapy regimes. Recently, it has been suggested that cancer cell-derived extracellular vesicles (EVs) could mediate drug resistance. In this study, the role of EVs in mediating the response of oral squamous cell carcinoma (OSCC) cells to cisplatin was investigated. We isolated and characterized EVs from OSCC cell lines showing differential sensitivities to cisplatin. Increased EV production was observed in both de novo (H314) and adaptive (H103/cisD2) resistant lines compared to sensitive H103 cells. The protein profiles of these EVs were then analyzed. Differences in the proteome of EVs secreted by H103 and H103/cisD2 indicated that adaptation to cisplatin treatment caused significant changes in the secreted nanovesicles. Intriguingly, both resistant H103/cisD2 and H314 cells shared a highly similar EV protein profile including downregulation of the metal ion transporter, ATP1B3, in the EVs implicating altered drug delivery. ICP-MS analysis revealed that less cisplatin accumulated in the resistant cells, but higher levels were detected in their EVs. Therefore, we inhibited EV secretion from the cells using a proton pump inhibitor and observed an increased drug sensitivity in cisplatin-resistant H314 cells. This finding suggests that control of EV secretion could be a potential strategy to enhance the efficacy of cancer treatment.

scholarly journals Nonsteroidal Anti-inflammatory Drugs Modulate Gene Expression of Inflammatory Mediators in Oral Squamous Cell Carcinoma

2019 ◽  
Vol 39 (5) ◽  
pp. 2385-2394
Author(s):  
DANIELLA MORAES ANTUNES ◽  
MARIA FERNANDA SETÚBAL DESTRO RODRIGUES ◽  
DOUGLAS MAGNO GUIMARÃES ◽  
CARINA MAGALHÃES ESTEVES DUARTE ◽  
LUCYENE MIGUITA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Inflammatory Mediators ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Therapeutic Efficacy Evaluation of Curcumin on Human Oral Squamous Cell Carcinoma Xenograft Using Multimodalities of Molecular Imaging

2010 ◽  
Vol 38 (02) ◽  
pp. 343-358 ◽  
Author(s):  
Yu-Chuan Lin ◽  
Hong-Wen Chen ◽  
Yu-Cheng Kuo ◽  
Ya-Fang Chang ◽  
Yi-Jang Lee ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Animal Model ◽  
Molecular Imaging ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Efficacy ◽  
Therapeutic Effects ◽  
Significant Difference

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity; however the treatment approaches are still unsatisfactory. We used a luciferase-transfected animal model to evaluate the therapeutic effects of curcumin. Human oral squamous cell carcinoma SAS cell line was stably transfected with luc gene, named SAS/luc cells. For the in vivo study, they were inoculated subcutaneously to 6-week-old male NOD/SCID mice which were separated into four groups for intraperitoneal injection (i.p.) of curcumin: control, daily with 35 mg/kg, 70 mg/kg every 2 days, and 100 mg/kg every 3 days. We applied SAS/luc bearing animal model and bioluminescent imaging (BLI) to study the inhibition effect of curcumin on tumor growth. The cytotoxic effect of curcumin on SAS/luc cells was mainly at G2/M phase and a significant dose dependent increase of the apoptotic SAS/luc cells as represented by sub-G1 phase was shown. Therapeutic efficacy evaluated by both caliper assay and BLI showed a significant difference between curcumin-treated mice and the controls (p < 0.01). The significant inhibition effects of curcumin on the proliferation and the growth of human OSCC are observed both in vitro and in vivo. No significant body weight change (i.e. within 20%) was observed in all SAS/luc-bearing mice with or without curcumin treatment. This SAS/luc human OSCC bearing animal model combined with multimodalities of molecular imaging permits a sensitive and non-invasive approach to evaluate the therapeutic efficacy in vivo.

scholarly journals Overexpression of fibronectin confers cell adhesion-mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells

2014 ◽  
Vol 44 (4) ◽  
pp. 1376-1384 ◽  
Author(s):  
YOSHIHIRO NAKAGAWA ◽  
HIDEKI NAKAYAMA ◽  
MASASHI NAGATA ◽  
RYOJI YOSHIDA ◽  
KENTA KAWAHARA ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Cell Adhesion ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Carcinoma Cells

scholarly journals LncRNA HOXA11-AS Promotes Proliferation and Cisplatin Resistance of Oral Squamous Cell Carcinoma by Suppression of miR-214-3p Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoyan Wang ◽  
Hong Li ◽  
Jing Shi
Keyword(s):  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Loss Of Function ◽  
Downstream Target ◽  
Xenograft Mice ◽  
Resistant Cells

Drug resistance to platinum limited therapeutic options for oral squamous cell carcinoma (OSCC). In the current study, we investigated the role of lncRNA HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS) in OSCC resistance to cisplatin (CDDP). We used clinical tissues and OSCC cell lines and induced CDDP resistance in OSCC cells. Gain and loss of function were performed in OSCC-resistant cells. Xenograft mice were also established. HOXA11-AS expression was increased in OSCC clinical tissues and cell lines and upregulated in CDDP-resistant cells. Upregulation of HOXA11-AS promoted proliferation in CDDP-sensitive cells and inhibited CDDP-induced cytotoxicity. In contrast, downregulation of HOXA11-AS decreased proliferation in CDDP-resistant cells and increased CDDP-induced cytotoxicity. Knockdown of HOXA11-AS inhibited the tumor growth in xenograft mice injected by CDDP. Downregulation of HOXA11-AS increased apoptosis and caspase 3 activities in CDDP-resistant OSCC cells. Bioinformatics, reporter assay, and loss and gain of function assay indicated that HOXA11-AS and miR-214-3p could negatively regulate each other. miR-214-3p was decreased in OSCC clinical tissues and cell lines. We further revealed that proto-oncogene serine/threonine-protein kinase (PIM1) was the target of miR-214-3p. PIM1 expression could be negatively regulated by miR-214-3p and positively regulated by HOXA11-AS. Inhibition of PIM1 suppressed anti-miR-214-3p-induced increase of cell proliferation and decrease of apoptosis. In summary, HOXA11-AS was identified to facilitate CDDP-resistance in OSCC and miR-214-3p/PIM1 was found to be the downstream target of HOXA11-AS. The findings highlight the importance of HOXA11-AS/miR-214-3p/PIM1 axis in the drug resistance of OSCC and provide potential targets for improving chemotherapy of OSCC.

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