Establishment of Drug-resistant Cell Lines as a Model in Experimental Oncology: A Review

Abstract

Many types of cancer are initially susceptible to chemotherapy, but during treatment, patients may develop resistance to therapy. Knowing that acquisition of drug resistance is a major clinical problem in antineoplastic treatment, the present work aimed to present, through a literature review, the development of chemoresistant cells lines as a model in experimental oncology. A total of 110 drugresistant cell lines, mainly from lung tumors and leukemias, have been developed. In addition, it has been observed that the drugs used for induction of resistance represented the drugs used for first-line treatment of each neoplasia, since the ideal chemotherapeutic treatment to induce resistance in vitro aims at a better modulation of the therapeutic response in order to better study the mechanisms of resistance. Normal tissue controls the production and release of growth promoting signals that regulate the initiation and progression of the cell cycle, ensuring cellular homeostasis and maintainance of healthy tissue architecture and function. Cancer cells exhibit deregulation of these signals and may acquire the ability to maintain continuous and abnormal proliferative signaling, inhibition of growth suppressors, resistance to cell death, replicative immortality, angiogenesis and metastasis that leads to an inadequate and pathogenic functioning of the tissue in which they occur (1-4). The literature shows that, in the tumor model, cancer cells originate from a single cell that has important stem cell characteristics, including the unlimited potential for replication and mechanisms of protection from xenobiotic agents. These findings have a significant effect on cancer treatment, since traditional antineoplastic treatment was based on the assumption that all somatic cells have a similar malignant potential, and the lack of specificity in combating these characteristics has rendered the therapies ineffective in providing a lasting response to cancer (5, 6). Chemotherapy is one of the pillars of clinical cancer treatment, but its outcome usually culminates in multidrug resistance (MDR), a phenomenon that can be found in several cells present in the tumor microenvironment, drastically restricting and the curative effect of drugs for a variety of tumors (7-9). Although many types of cancer are initially susceptible to chemotherapy, over the course of the therapeutic regimen, some patients may develop therapeutic resistance, due to several intracellular mechanisms including genetic and epigenetic changes in signaling pathways of survival, drug metabolizing enzymes and drug efflux pump mechanisms. Epigenetic modifications also act as an important set of mechanisms that lead to resistance in cancer treatment, and the main ones include DNA methylation and histone acetylation that can influence carcinogenesis because they deregulate normal expression of genes (Figure 1) (10, 11). The most studied mechanism of resistance to drugs against cancer involves the reduction of the intracellular concentration of the drug by increasing drug ...

Microgreens: Functional Food with Antiproliferative Cancer Properties Influenced by Light

“…However, taking into consideration that the same microgreen extracts impacted differently on cell proliferation between RD-ES and A673 in 2D models highlights the need for screening different cancer cell lines when testing for ameliorative effects of food matrixes and phytochemical compounds. Of interest, constraints pertaining to the physical micro-environment of spheroids as well as accompanying epigenetic effects have also been shown to render tumors resistant to cancer drug treatments in clinical settings [19,20,34,35]. Hence, there is the requisite for research into the efficacy of dietary phytochemicals in mitigating constraints related to the physical micro-environment of spheroids and epigenetic modifications [17,20,[33][34][35].…”

“…Of interest, constraints pertaining to the physical micro-environment of spheroids as well as accompanying epigenetic effects have also been shown to render tumors resistant to cancer drug treatments in clinical settings [19,20,34,35]. Hence, there is the requisite for research into the efficacy of dietary phytochemicals in mitigating constraints related to the physical micro-environment of spheroids and epigenetic modifications [17,20,[33][34][35]. This approach may be particularly attractive for rare, hard-totreat cancer lines such as Ewing sarcoma, displaying resistance mechanisms [21,36], where, although nutraceutical supplementation is sought-after for patients, there is a requisite for phytochemicals with strictly pro-oxidant activity [37].…”

Generation of Two Paclitaxel-Resistant High-Grade Serous Carcinoma Cell Lines With Increased Expression of P-Glycoprotein

“…In the majority of established chemoresistant cell lines, Cisplatin is the drug mostly used for the induction of resistance (26). PTX-resistance induction is less commonly accessible, being established in gastric adenocarcinoma (OCUM-2M/PTX), breast cancer (MCF7/TAX), and prostate cancer (DU145-TxR, PC-3-TxR) models (27)(28)(29).…”

Modulated Electro-Hyperthermia Supports the Effect of Gemcitabine Both in Sensitive and Resistant Pancreas Adenocarcinoma Cell Lines

“…GEM-resistant cell lines were established using cell selection method [21]. Briefly, cells were exposed to increasing concentrations of GEM starting from 0.05 nM for Capan1 and 1 nM for Panc1.…”