The role of microenvironmental pH regulation on colorectal cancer cells - a preliminary study

The pH gradient inversion is one of the characteristic features of cancer cells. The acidic environment outside the tumor and the alkaline inside cancer cells significantly affect its growth and ability to metastasize and reduce the effectiveness of therapy. In this study, we examined the effect of the alkaline pH on the viability of colorectal cancer (CRC) cells Caco-2 and Ht-29, and normal human fibroblasts BJ-CRL-2522 as a control cell line. Moreover, we analyzed the expression level of 3 genes at different pH: pro-apoptotic BAX, proliferation marker MKI67, and pH-sensitive receptor GPR4 using the RT-qpCR method. We demonstrated increased Ht-29 cell viability at alkaline pH, with simultaneous morphological changes, and decreased Caco-2 cell viability at pH above 9. The expression of BAX, GPR4 was upregulated in Ht-29 and BJ cells cultured at alkaline pH, whereas in Caco-2 cells the expression was significantly different between conditions. MKI67 expression was slightly increased in HT-29 and BJ, while decreased in Caco-2 cells. Our study shed new light on the cellular processes occurring under the influence of alkalization, but it is difficult to assess what role alkalization may play in the potential therapy of CRC, therefore, further studies are necessary.