Paclitaxel induces apoptosis and reduces proliferation by targeting epidermal growth factor receptor signaling pathway in oral cavity squamous cell carcinoma

Hu, Jing; Zhang, N A; Wang, Ronglin; Huang, Fei; Li, Guang

doi:10.3892/ol.2015.3499

Cited by 20 publications

(15 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is noted that up-regulation of fibronectin coincided with the reduced uptake of DOX at higher concentration (300 μM) in co-cultured TSs ( Fig 4C ). These results are in agreement with previous reports in which increased stiffness caused by increased ECM deposition in tumor tissue was suggested as a physical barrier preventing intratumoral drug penetration [ 46 ]. Collectively, our model may serve as a useful model in investigating CAF-induced and ECM-related drug resistance as well as EMT in 3D tumors.…”

Section: Discussionsupporting

confidence: 94%

Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment

et al. 2016

View full text Add to dashboard Cite

Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a ‘more clinically relevant’ tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip-based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono-cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in α-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation.

show abstract

Section: Discussionsupporting

confidence: 94%

Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Paclitaxel induces apoptosis in various tumor types and regulates different signaling mechanisms in each ( 12 , 17 , 36 ). The AKT/MAPK signaling pathway is hypothesized to have a role in sensitivity to paclitaxel and serve as a potential therapeutic target for treatment of gastric cancer ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

“…Surgical resection and chemotherapy are the most commonly used methods of clinical treatment of mammary gland tumors ( 3 – 5 ). Paclitaxel belongs to the class of diterpenoid compounds (mitotic inhibitors) derived from Taxus brevifolia , exerting efficient, broad-spectrum chemotherapeutic effects against various cancer types, including human ovarian cancer ( 6 , 7 ), breast cancer ( 8 , 9 ), gastric cancer ( 10 ) and other malignancies ( 11 , 12 ). The molecular formula of paclitaxel is C 47 H 51 NO 14 and the relative molecular mass is 853.890.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have demonstrated that chemotherapeutic drugs control growth of cancerous tissue through induction of apoptosis ( 10 , 12 , 13 , 15 ). Therefore, the assessment of apoptosis following treatment with a novel chemotherapeutic drug is a marker of efficacy ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the assessment of apoptosis following treatment with a novel chemotherapeutic drug is a marker of efficacy ( 16 ). Paclitaxel induces apoptosis in multiple cell types through different signal transduction pathways, including the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) pathway ( 17 ), the epidermal growth factor receptor pathway ( 12 ), and the mitogen-activated protein kinase (MAPK) pathway ( 18 ). Targeted inhibition of phosphorylated-phosphatidylinositol-3-kinase (p-PI3K) was demonstrated to enhance the induction of apoptosis and increase the sensitivity of paclitaxel-resistant ovarian cancer cells to treatment ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells

et al. 2018

View full text Add to dashboard Cite

Paclitaxel is a diterpenoid compound, derived from the pacific yew (Taxus brevifolia) berry, which exhibits antineoplastic effects against various types of cancer. However, the antitumor effects and the molecular mechanisms of paclitaxel on canine CHMm cells remain to be elucidated. The aim of the present study was to investigate the antitumor effects of paclitaxel on CHMm cells and identify relevant signal transduction pathways modulated by paclitaxel using multiple methods including MTT assay, flow cytometry, acridine orange/ethidium bromide staining, transmission electron microscopy, determination of cellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondiadehyde (MDA) and western blotting, the data indicated that paclitaxel decreased cell viability, induced G2/M-phase cell cycle arrest, suppressed the expression of cyclin B1 and induced apoptosis in a dose-dependent manner. In addition, paclitaxel upregulated the expression of Bax and cytochrome c, but reduced expression of apoptosis regulator Bcl-2, resulting in activation of caspase-3, chromatin condensation, karyopyknosis, intracellular vacuolization, increased production of ROS and MDA, and decreased activity of SOD. However, these effects were inhibited when CHMm cells were treated with N-acetyl-L-cysteine. Furthermore, treatment with paclitaxel inhibited the level of of phospho (p)-RAC-α serine/threonine-protein kinase (AKT) and p-ribosomal protein S6 kinase proteins, and promoted phosphorylation of P38 mitogen-activated protein kinase (MAPK) and p-90 kDa ribosomal protein S6 kinase 1 proteins in CHMm cells. It was observed that paclitaxel in combination with pharmacological inhibitors of the P38 and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathways (SB203580 and LY294002, respectively) exerted synergistic inhibitory effects on the proliferation of the CHMm cells. The results of the present study demonstrated that paclitaxel inhibited tumor cell proliferation by increasing intrinsic apoptosis through inhibition of the PI3K/AKT signaling pathway and activation of MAPK signaling pathway in CHMm cells.

show abstract

Ex Vivo Tumor‐on‐a‐Chip Platforms to Study Intercellular Interactions within the Tumor Microenvironment

Kumar

Varghese

2018

Adv Healthcare Materials

View full text Add to dashboard Cite

The emergence of immunotherapies and recent FDA approval of several of them makes them a promising therapeutic strategy for cancer. While these advancements underscore the potential of engaging the immune system to target tumors, this approach has so far been efficient only for certain cancers. Extending immunotherapy as a widely acceptable treatment for various cancers requires a deeper understanding of the interactions of tumor cells within the tumor microenvironment (TME). The immune cells are a key component of the TME, which also includes other stromal cells, soluble factors, and extracellular matrix‐based cues. While in vivo studies function as a gold standard, tissue‐engineered microphysiological tumor models can offer patient‐specific insights into cancer‐immune interactions. These platforms, which recapitulate cellular and non‐cellular components of the TME, enable a systematic understanding of the contribution of each component toward disease progression in isolation and in concert. Microfluidic‐based microphysiological platforms recreating these environments, also known as “tumor‐on‐a‐chip,” are increasingly being utilized to study the effect of various elements of TME on tumor development. Herein are reviewed advancements in tumor‐on‐a‐chip technology that are developed and used to understand the interaction of tumor cells with other surrounding cells, including immune cells, in the TME.

show abstract

Paclitaxel induces apoptosis and reduces proliferation by targeting epidermal growth factor receptor signaling pathway in oral cavity squamous cell carcinoma

Cited by 20 publications

References 25 publications

Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment

Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment

Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells

Ex Vivo Tumor‐on‐a‐Chip Platforms to Study Intercellular Interactions within the Tumor Microenvironment

Contact Info

Product

Resources

About