Abstract
BackgroundCell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed.MethodsA novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs.ResultsIt was confirmed in this present study that the IC50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI100. Additionally, the GR100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared.ConclusionSince the GR100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR100 of a particular anti-cancer drug can be used to effectively assess the resistance.
Highlights
Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible
The IC50 has no clinical significance in this type of experiment because it indicates the concentration of a drug that has caused a 50% reduction in cell number compared to a control group that has not been treated (Fig. 1A)
The Normalized growth rate inhibition (GR) system is a method of representing Growth inhibition (GI) by calibrating the doubling time problem associated with the Inhibitory concentration (IC) (Fig. 1B) [8,10]
Summary
Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. The IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. This can be determined by evaluating the growth rate from the seeding cells, and utilizing the GI instead of the IC (Fig. 1A) [9].
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