Promising applications of nanotechnology in inhibiting chemo-resistance in solid tumors by targeting epithelial-mesenchymal transition (EMT)

Tangsiri, Mona; Hheidari, Ali; Liaghat, Mahsa; Razlansari, Mahtab; Ebrahimi, Narges; Akbari, Abdullatif; Varnosfaderani, Seyed Mostafa Noorbakhsh; Maleki-Sheikhabadi, Fahimeh; Norouzi, Ali; Bakhtiyari, Maryam; Zalpoor, Hamidreza; Nabi-Afjadi, Mohsen; Rahdar, Abbas

doi:10.1016/j.biopha.2023.115973

Cited by 9 publications

(4 citation statements)

References 154 publications

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“…In fact, VCAM1 has been suggested as a factor in estimating poor patient prognosis and can promote tumor metastasis by inducing EMT in cancer [70]. In pancreatic cancer, EMT is known to lead to acquiring the characteristics of cancer stemness and enhance chemotherapy resistance through multiple different ways [71]. For instance, it is reported that the recapitulation of the fibrotic rigidities in pancreatic cancer tissues promotes elements of EMT, and the stiffness induces chemoresistance in pancreatic cancer cells [72].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Epithelial–Mesenchymal Transition Is a Possible Underlying Mechanism for Inducing Chemoresistance in MIA PaCa-2 Cells against Gemcitabine and Paclitaxel

Nakamura,

Watanabe,

Takada

et al. 2024

Biomedicines

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To elucidate the currently unknown molecular mechanisms responsible for the similarity and difference during the acquirement of resistance against gemcitabine (GEM) and paclitaxel (PTX) in patients with pancreatic carcinoma, we examined two-dimensional (2D) and three-dimensional (3D) cultures of parent MIA PaCa-2 cells (MIA PaCa-2-PA) and their GEM resistance cell line (MIA PaCa-2-GR) and PTX resistance (MIA PaCa-2-PR). Using these cells, we examined 3D spheroid configurations and cellular metabolism, including mitochondrial and glycolytic functions, with a Seahorse bio-analyzer and RNA sequencing analysis. Compared to the MIA PaCa-2-PA, (1) the formation of the 3D spheroids of MIA PaCa-2-GR or -PR was much slower, and (2) their mitochondrial and glycolytic functions were greatly modulated in MIA PaCa-2-GR or -PR, and such metabolic changes were also different between their 2D and 3D culture conditions. RNA sequencing and bioinformatic analyses of the differentially expressed genes (DEGs) using an ingenuity pathway analysis (IPA) suggested that various modulatory factors related to epithelial –mesenchymal transition (EMT) including STAT3, GLI1, ZNF367, NKX3-2, ZIC2, IFIT2, HEY1 and FBLX, may be the possible upstream regulators and/or causal network master regulators responsible for the acquirement of drug resistance in MIA PaCa-2-GR and -PR. In addition, among the prominently altered DEGs (Log2 fold changes more than 6 or less than −6), FABP5, IQSEC3, and GASK1B were identified as unique genes associated with their antisense RNA or pseudogenes, and among these, FABP5 and GASK1B are known to function as modulators of cancerous EMT. Therefore, the observations reported herein suggest that modulations of cancerous EMT may be key molecular mechanisms that are responsible for inducing chemoresistance against GEM or PTX in MIA PaCa-2 cells.

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Section: Discussionmentioning

confidence: 99%

Modulation of Epithelial–Mesenchymal Transition Is a Possible Underlying Mechanism for Inducing Chemoresistance in MIA PaCa-2 Cells against Gemcitabine and Paclitaxel

Nakamura,

Watanabe,

Takada

et al. 2024

Biomedicines

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“…Solid tumors (such as pancreatic, breast, prostate, and other cancers) account for the vast majority of cancer cases and deaths. , They are confronted with a hypoxic and nutrient-deficient microenvironment. Thus, hypoxic tumor cells increase the expression of nutrient transporters and pH regulators simultaneously in order to adapt and meet their bioenergetic and biosynthetic demands .…”

Section: Introductionmentioning

confidence: 99%

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR-2 as Potential Agents for Solid Tumors: X-ray, In Vitro, In Vivo, and In Silico Investigations of Coumarin-Based Thiazoles

Hefny,

El-Moselhy,

El-Din

et al. 2024

J. Med. Chem.

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A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a−h, 6, and 7a−e) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a, 5d, and 5e can effectively inhibit both targets. 5a, 5d, and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5e to interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivo efficacy of compound 5e as an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5e and CA IX and VEGFR-2 binding pockets.

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“…To address these challenges, innovative approaches such as targeted therapies are being explored. These therapies allow for the local administration of drugs in higher concentrations, minimizing systemic toxicity and improving patient survival [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Currently, anti-cancer drugs like 5-fluorouracil, paclitaxel, cisplatin, and docetaxel are used in oral cancer treatment [ 47 , 48 ].…”

Section: Introductionmentioning

confidence: 99%

Application of Scaffold-Based Drug Delivery in Oral Cancer Treatment: A Novel Approach

Saberian,

Jenča,

Petrášová

et al. 2024

Pharmaceutics

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This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, notably those coated with anti-cancer agents such as cisplatin and paclitaxel, have proven effective in inhibiting oral cancer cell proliferation, establishing a promising avenue for site-specific drug delivery. The application of synthetic scaffolds, including Poly Ethylene Glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA), and natural materials, like collagen or silk, in 3D systems has been pivotal for controlled release of therapeutic agents, executing diverse anti-cancer strategies. A key advancement in this field is the advent of smart scaffolds designed for sequential cancer therapy, which strive to refine drug delivery systems, minimizing surgical interventions, accentuating the significance of 3D scaffolds in oral cancer management. These systems, encompassing local drug-coated scaffolds and other scaffold-based platforms, hold the potential to transform oral cancer treatment through precise interventions, yielding improved patient outcomes. Local drug delivery via scaffolds can mitigate systemic side effects typically associated with chemotherapy, such as nausea, alopecia, infections, and gastrointestinal issues. Post-drug release, scaffolds foster a conducive environment for non-cancerous cell growth, adhering and proliferation, demonstrating restorative potential. Strategies for controlled and targeted drug delivery in oral cancer therapy span injectable self-assembling peptide hydrogels, nanocarriers, and dual drug-loaded nanofibrous scaffolds. These systems ensure prolonged release, synergistic effects, and tunable targeting, enhancing drug delivery efficiency while reducing systemic exposure. Smart scaffolds, capable of sequential drug release, transitioning to cell-friendly surfaces, and enabling combinatorial therapy, hold the promise to revolutionize treatment by delivering precise interventions and optimized outcomes. In essence, scaffold-based drug delivery systems, through their varied forms and functionalities, are reshaping oral cancer therapy. They target drug delivery efficiency, diminish side effects, and present avenues for personalization. Challenges like fabrication intricacy, biocompatibility, and scalability call for additional research. Nonetheless, the perspective on scaffold-based systems in oral cancer treatment is optimistic, as ongoing advancements aim to surmount current limitations and fully leverage their potential in cancer therapy.

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Promising applications of nanotechnology in inhibiting chemo-resistance in solid tumors by targeting epithelial-mesenchymal transition (EMT)

Cited by 9 publications

References 154 publications

Modulation of Epithelial–Mesenchymal Transition Is a Possible Underlying Mechanism for Inducing Chemoresistance in MIA PaCa-2 Cells against Gemcitabine and Paclitaxel

Modulation of Epithelial–Mesenchymal Transition Is a Possible Underlying Mechanism for Inducing Chemoresistance in MIA PaCa-2 Cells against Gemcitabine and Paclitaxel

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR-2 as Potential Agents for Solid Tumors: X-ray, In Vitro, In Vivo, and In Silico Investigations of Coumarin-Based Thiazoles

Application of Scaffold-Based Drug Delivery in Oral Cancer Treatment: A Novel Approach

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