PDTC inhibits apoptosis and phenotypic transformation of co-culture of myeloma cells and renal tubular epithelial cells by reducing the secretion of light chain protein

Background The human myeloma cell line RPMI-8226 is co-cultured with human proximal tubular epithelial cell HK-2, which is commonly used to simulate the renal environment in patients with multiple myeloma. This study aimed to investigate the effects of NFκB inhibitor PDTC on the viability, apoptosis and cell phenotype of HK-2 cells in the co-culture system of myeloma cells in renal tubular epithelial cells.Methods An in vivo environment was simulated through a cell co-culture system. RPMI-8226 cells and HK-2 cells were inoculated in the co-culture chamber and cultured for 24 h to establish the co-culture system. PDTC was used in the single culture group and the co-culture group, respectively. The activity of HK-2 cells and RPMI-8226 cells in each group was detected by MTT. An immunoturbidimetric assay was performed to assess the effect of PDTC on secretion of κ light chain and λ light chain in RPMI-8226 cells. Flow cytometry was used to detect apoptosis of HK-2 cells. Western blot was carried out to detect NF-κB activation in RPMI-8226 myeloma cells, as well as the expression levels of caspase-3, bcl-2, Bax, E-cadherin, and α-SMAin HK-2 cells. Caspse-3 assay kit was used to detect the activity of caspase-3. The effect of PDTC on the secretion of κ light chain and λ light chain of RPMI-8226 cells was detected by immunoturbidimetry and the ratio was calculated.Results PDTC had a potent inhibitory effect on proliferation of RPMI-8226 cells in a dose- and time-dependent manner. PDTC had no significant effect on the viability of HK-2 cells cultured alone, and the addition of PDTC to the co-culture system significantly increased the viability of HK-2 cells. PDTC did not significantly change the apoptosis of HK-2 cells cultured alone, but could reduce the apoptosis of renal tubular epithelial cells by regulating the activity of caspase3 and the ratio of bcl2/bax in HK-2 cells in the co-culture system. After PDTC treatment, the expression of cell surface marker E-cadherin decreased, and the expression of α-SMA increased, which induced the renal interstitial fibrosis. The secretion of κ light chain and λ light chain of RPMI-8226 cells was significantly decreased after the addition of PDTC, but the ratio was not changed.Conclusions PDTC can inhibit the cell activity, promote apoptosis, and reduce the secretion of secretion of κ light chain and λ light chain through inhibiting the NF-κB pathway activation of myeloma cell RPMI-8226, leading to increased activity of renal tubular epithelial cells HK-2 in the co-culture system, decreased apoptosis, and renal interstitial fibrosis.