Panoply™ Human PDPK1 Knockdown Stable Cell Line

Epithelial ovarian cancer (EOC) is a common estrogen-sensitive tumor that seriously threatens women's health, and its mortality rate ranks first among female malignant tumors. Studies have shown that estrogen abnormalities are closely related to the progression of EOC. 3-phosphoinositide-dependent protein kinase-1 (PDPK1) is highly expressed in EOC tissues. Furthermore, estrogen can upregulate the expression of PDPK1 in EOC cells. Here, researchers found that high expression of PDPK1 is associated with poor prognosis in ovarian cancer patients. In addition, estrogen stimulates the increased expression of PDPK1 protein through the estrogen receptor ESR1. The absence or overexpression of PDPK1 affects the inhibition or enhancement of estrogen-driven EOC cell proliferation, while knockdown of PDPK1 can inhibit estrogen-induced EOC cell migration and promote apoptosis. This indicates an important functional link between estrogen and PDPK1 in the development and progression of EOC. Under estrogen treatment, PDPK1 can regulate the messenger RNA expression of cyclin A1, cyclin-dependent kinase 2 (CDK2), matrix metalloproteinase 2 (MMP2), and Bcl-2-associated X protein (Bax). These findings suggest that PDPK1 plays an oncogenic role in the development and progression of EOC.

To elucidate the role of PDPK1 in E2-induced SK-OV-3 cells, researchers examined the physiological functions of PDPK1-knockdown SK-OV-3 cells under E2 stimulation, including changes in cell proliferation, migration, and apoptosis levels. The researchers used EdU staining to detect the effect of PDPK1 on the proliferation of E2-stimulated SK-OV-3 cells. The results showed that E2 significantly promoted the proliferation of SK-OV-3 cells (Figure 1B and b). In contrast, in PDPK1-knockdown SK-OV-3 cells, the proliferative effect of E2 was inhibited. Subsequently, cell migration experiments showed that E2 significantly promoted the migration of SK-OV-3 cells; however, in PDPK1-knockdown cells, the migration-promoting effect of E2 was inhibited (Figure 1C and c). Since the above results indicated that the absence of PDPK1 inhibited E2-induced SK-OV-3 cell proliferation and migration, the researchers used flow cytometry to detect the potential role of E2 and PDPK1 in altering SK-OV-3 cell apoptosis. They found that E2 induced late apoptosis (Figure 1D and d), while interfering with PDPK1 exacerbated late apoptosis and cell death. In summary, these results indicate that E2 exhibits significant pro-cancer effects in SK-OV-3 cells in a PDPK1-dependent manner.

Figure 1. Knock-down of PDPK1 suppresses E2-driven SK-OV-3 cells proliferation and migration but promotes apoptosis. (Wang Y, et al., 2024)