Substrate stiffness influences the outcome of antitumor drug screening in vitro

Substrate stiffness has been proven to play a critical role in vitro tumor proliferation; however, pharmacological studies on antitumor drug screening are still routinely carried out in regular plastic culture plates. In the article, polydimethylsiloxane (PDMS) substrates with different stiffness (mimicking articular cartilage, collagenous bone and mammary tumor respectively) and plastic substrate were employed to establish the mechanical microenvironment for the in vitro drug screening platform. We studied the influences of stiffness on the responses of MCF-7 cells to typical antitumor drugs, cisplatin and taxol. Results showed that for both the treatment IC50 value to MCF-7 cells decreased significantly (p < 0.01) on the rigid substrate, indicating that MCF-7 cells on soft substrate have a resistance to cytotoxicity of antitumor drugs. The sensitivity of MCF-7 cells on rigid substrate to drug cytotoxicity was attributed to the increased cell cycle progression, implying that agents proven to be effective in vitro by conventional screening approach might be inefficient in a soft microenvironment in vivo. We conclude that stiffness of the substrates, as a critical mechanical factor, should be concerned for screening antitumor agents in vitro. As an extrapolation, the extensively used drug screening system needs to be revalued and redesigned.