Panoply™ Human CD24 Knockdown Stable Cell Line

Breast cancer (BC) is the leading cause of cancer-related death in women. Drug resistance is the main cause of treatment failure. Notably, some reports have shown that the cell surface biomarker CD44+/CD24- is associated with drug resistance, but the underlying mechanism is unclear. Here, researchers explored the potential role of CD24 expression in docetaxel or doxorubicin resistance using triple-negative breast cancer (TNBC) tissue microarray. In addition, in vitro experiments were performed to evaluate the changes in CD24 expression and differential drug sensitivity after chemotherapy. In addition, mouse tumor xenograft studies were performed to validate the in vitro findings. Overall, the results showed that CD24-positive TNBC patients had significantly shortened overall survival and disease-free survival after taxane treatment. In addition, in vitro cell studies showed that CD44+/CD24+/high-expressing cells were more resistant to docetaxel, while CD44+/CD24-/low-expressing cells were more resistant to doxorubicin. Both in vitro and in vivo studies have shown that CD24 knockdown cells are more sensitive to docetaxel, while CD24 overexpressing cells are more sensitive to doxorubicin. In addition, mechanistic studies have shown that Bcl-2 and TGF-βR1 signaling regulate CD24 through the ATM-NDRG2 pathway. Therefore, CD24 may become a biomarker for selecting chemotherapeutic drugs and a target for overcoming drug resistance in triple-negative breast cancer (TNBC).

After knockdown of CD24 in 3D culture, HCC1806 cells were more sensitive to docetaxel (Figure 1A). In contrast, cells with knockdown of NDRG2 showed enhanced resistance to docetaxel and were more sensitive to doxorubicin. Similar results were observed in another cell line, HCC1937, with knockdown of CD24 expression (Figure 1B). In contrast, overexpression of CD24 in HCC1806 increased doxorubicin sensitivity (Figures 1C and 1D), consistent with the results of enhancing CD24 by inhibiting the CD24 inhibitor NDRG2. Next, the researchers conducted in vivo studies in tumor xenograft models. As shown in Figures 1E and 1F, compared with the control group, the TNBC HCC1806 tumor xenografts with NDRG2 knockdown had significantly smaller tumors after doxorubicin treatment. On the other hand, compared with the control group, the tumors of the CD24 knockdown HCC1806 cell line were significantly reduced after docetaxel treatment (Figure 1G). Another CD24 knockdown MDA-MB-231 cell line also showed enhanced tumor response to docetaxel (Figure 1H), which was consistent with the results predicted by in vitro data. Statistical analysis of tumor shrinkage under different conditions showed that inhibiting CD24 reduced docetaxel resistance, while increasing CD24 or inhibiting CD24 increased docetaxel sensitivity (Figure 1I). These results suggest that targeting or regulating CD24 expression may help overcome TNBC resistance.

Figure 1. Targeting CD24 and its inhibitor gene NDRG2 by shRNAs improved chemotherapy sensitivity in vitro and in vivo. (Deng X, et al., 2017)