Fig. 2

Notch inhibition decreased the self-renewal ability of Erlotinib resistant cells and re-sensitized the resistant cells to Erlotinib. A The addition of Erlotinib decreased the ALDH1A1 positive cells of PC9 and HCC827 cells significantly, but did not affect the ratios of Erlotinib resistant PC9ER and HCC827ER cells. B The addition of Erlotinib decreased the spheres number of PC9 and HCC827 cells significantly, but did not affect the number of Erlotinib resistant PC9ER and HCC827ER cells. C Representative images of ALDEFLUOR isolation were detailed exhibited. Two kinds of Notch signaling inhibitors, FLI-06 (inhibitor-1), and γ-Secretase inhibitor (inhibitor-2) were used. 200 nM of inhibitor-1 (D) decreased the self-renewal ability of multiple kinds of lung cancer cells, and 50 nM of inhibitor-2 (E) decreased the self-renewal ability of multiple kinds of lung cancer cells. F Notch signaling inhibition decreased the stem cells’ ratio of the Erlotinib resistant cells significantly, and further, the much-lowered concentration of Notch signaling inhibitor-1, the 20 nM of FLI-06 sensitized both PC9ER and HCC827ER cells to Erlotinib treatment greatly. Erlotinib alone inhibited the Notch signaling slightly, and lowered concentration of FLI-06 mildly inhibited the Notch signaling, but effectively enhanced the Erlotinib functions in PC9ER (Fig. 3G) and HCC827ER cells (Fig. 3H). Combined TUSC7 and Erlotinib decreased the stem cells ratio greatly in both PC9ER and HCC827ER cells (Fig. 3I-J). K-L The stem cells’ renewal suppression evaluation did not show significant differences between TUSC7 alone and the combination of TUSC7 and FLI-06