FLCN reversely regulated paclitaxel-induced autophagy via the ERK 1/2 pathway. A. ERK 1/2 pathway was activated in UOK257 and ACHN-5968 cells. Both P-MEK and P-ERK were increased those cells. B. Western Blot analysis showed that both P-ERK and Beclin 1 proteins were significantly elevated in FLCN-deficient cells after paclitaxel, compared to controls. C. ERK inhibitor U0126 repressed the expression of LC3-II protein in FLCN-deficient cells. D. Fewer punctuated dots were detected in GFP-LC3 transfected FLCN-deficient cells after treatment of paclitaxel and U0126 (*: p < 0.05, UOK257 + Paclitaxel vs UOK257 + Paclitaxel + U0126; ACHN 5968 + Paclitaxel vs ACHN 5968 + Paclitaxel + U0126; n = 60). Scale bars = 15 μm. E. Treatment with U0126 further enhanced preferential toxicity of paclitaxel to FLCN-deficient cells (*: p < 0.05. UOK257 + Paclitaxel vs UOK257 + Paclitaxel + U0126; ACHN 5968 + Paclitaxel vs ACHN 5968 + Paclitaxel + U0126; n = 15). After treatment with U0126, apoptosis induced by paclitaxel was significantly increased in FLCN-deficient UOK257 and ACHN-5968 cells (*: p < 0.05. UOK257: Paclitaxel vs Paclitaxel + U0126; ACHN 5968: Paclitaxel vs Paclitaxel + U0126; n = 15).