Drug Resistant Cells
Publications describing the development of an anti-cancer drug-resistant in vitro model, which exhibited acquired resistance to a chemotherapy drug, was first published in 1970. However, publications in this research field usually place little emphasis on how the drug-resistant cell lines were established in the laboratory. The development of drug-resistant cell lines can take anything from 3 to 18 months in the laboratory and many decisions are taken along this process, such as the choice of parent cell line, dose of selecting agent, and the treatment interval.
Laboratory drug-resistant cell models are established with the aim of understanding the underlying mechanisms of toxicity and resistance to chemotherapy agents. Cells are usually grown continually in the presence of drugs and highly drug-resistant clones are selected from a mixed population. Drug dosages tend to be high and the therapeutic doses escalate over time.
Laboratory drug-resistant cell models are generally more stably resistant and therefore easier to maintain in culture for an ongoing research project. Levels of resistance are often higher, so the molecular changes associated with the resistant mechanism are greater and easier to identify. It is common to have difficulty to develop stable clinically relevant drug-resistant cell lines. However, a comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents alleviates this risk and gives insight into which agents or type of cell line develops resistance easily.
Figure 1. Mechanism involved in tumor MDR.
H69 Drug-resistant Cell Model
We have derived a number of human lung cancer cell sublines with acquired resistance to cytotoxic drugs. They are being used as model systems for studying resistance circumvention strategies. Small cell lung cancer subline H69/LX4 is a classic multidrug resistant (MDR) cell line that hyper-expresses P-glycoprotein and shows a drug accumulation deficit. Although MDR phenotype induced by doxorubicin are not generally resistant to cisplatin, there is no doubt that both inherent and acquired resistance to cisplatin are significant clinical problems. Therefore, we set out to produce cisplatin-resistant lung cancer cell sublines by treating cells in culture with cisplatin. Over a prolonged period, we succeeded in deriving sublines H69/CPR, which can grow continuously in cisplatin. Such cell lines are extremely valuable for studying basic mechanisms in the laboratory and also for developing molecular and antibody probes for these mechanisms which can be subsequently used to investigate clinical material.
A2780 Drug-resistant Cell Model
Ovarian cancer is the most lethal gynecological cancer in which chemotherapy-based treatment plays a fundamental role as the first-line option. However, development of drug-resistance is a critical and poorly understood problem in ovarian cancer treatment. For many years, the A2780 series of ovarian cancer cell lines have been effective in vitro tools for cancer research. A2780/cis and A2780/ADR are resistant to cisplatin and doxorubicin respectively. They play an important role in the study of cancer biology and chemo-resistance, enabling the search for new treatments. Drug resistance has been quantified in these cell lines by using IC50 values, the dose of a drug causing a 50% inhibition in normal cell growth.
MCF-7 Drug-resistant Cell Model
MCF-7 human breast cancer cells provide a useful in vitro modeling system for studying hormone-responsive breast cancer as they contain receptors for estrogen and progesterone that induce the synthesis of specific proteins and increase their rate of proliferation. MCF7/TAMR-7 is a breast cancer cell line resistant to tamoxifen, and the parental cell line is MCF7/S0.5. MCF7/TAMR-7 has been established from a clone of cells that survived for a long time under 1 µM of tamoxifen. Tamoxifen is the most widely used drug for the treatment of hormone-dependent breast cancer. However, primary or acquired resistance to tamoxifen severely limits its clinical efficacy. The MCF7/TAMR-7 cell line is a good model to study the signaling pathways, which are the major drivers of tamoxifen-resistant growth.
Description: The MCF7/TAMR-7 Cell line is a breast cancer cell line resistant to tamoxifen. Tamoxifen is by far ...
Description: COR-L23/5010 has been derived from the parent line, COR-L23 by continuous exposure to increasing ...
Description: The cell line COR-L23/CPR is a drug-resistant variant of COR-L23. The line was developed by growing ...
Description: The cell line COR-L23/R is a multi-drug resistant (MDR) sub-line derived from the parent line ...
Description: The revertant lung cancer cell line COR-L23/R23- was generated by growing the doxorubicin-selected, ...
Description: The drug resistant cell line MOR/0.2R has been derived from the parent line, MOR, by continuous ...
Description: MOR/0.4R has been developed from the parent line, MOR, by continuous exposure to increasing ...
Description: MOR/CPR has been developed by growing the parent line, MOR, in increasing concentrations of ...
Description: The adriamycin-resistant cell line A2780ADR has been developed by exposure of the parent A2780 cell ...
Description: This cisplatin-resistant cell line has been developed by chronic exposure of the parent ...
Description: The multi drug-resistant cell line MES-SA/Dx5 was derived from the human uterine sarcoma cell line ...
Description: The drug resistant cell line K562 AZQ has been developed from the parent K562 cell line by ...
Description: This Adriamycin-resistant cell line has been developed by exposure of the parent L929 murine ...
Description: Derived from a female BALB/c myeloma tumour MPC-11. The parental cell line has mutated during ...
Description: A 6-thioguanine resistant mutant of mouse L cell fibroblasts (Mouse strain C3H/An). A9 lacks ...
Description: An 8-bromodeoxyuridine resistant mutant of mouse L cell fibroblasts (Mouse strain C3H/An). B82 ...
Description: EMT6/AR1 was derived from the mouse mammary tumour cell line EMT6/P by growth in increasing amounts ...
Description: The drug resistant cell line EMT6/AR10.0 was derived from the mouse mammary tumour cell line EMT6/P ...