Tetrandrine(μM): 6 6 6 6 Sorafenib(μM): 0 3 4 5 Tetrandrine(μM): 0 4 5 6 Sorafenib(μM): 4 4 4 4 A B S 1 Cell viability for the combination of sorafenib.

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Tetrandrine(μM): Sorafenib(μM): Tetrandrine(μM): Sorafenib(μM): A B S 1 Cell viability for the combination of sorafenib and tetrandrine in various concentrations

BEL7402 S 2 Dose-response curves and combination index values (CI ﹤ 1 ) showed the synergistic effect of combination with sorafenib and tetrandrine was existed

Cell cycle for combination of sorafenib and tetrandrine showed no significant alteration S 3 HCT116 BEL7402 ConTet+BayTetBay

Sor －＋－＋ Tet －－＋＋ * Activation of caspase-3 and caspase-9 in BEL7402 cells was determined after treatment with sorafenib and/or tetrandrine for 24 h S 4

S 5 The body weights of nude mice bearing established HCT116 tumor xenografts

GAPDH BEL7402HCT116 Sor －＋－＋－＋－＋ Tet －－＋＋－－＋＋ LC3- Ⅰ LC3- Ⅱ Cell viability could not be rescued by the autophagy inhibitor 3-methyladenine (3-MA) or chloroquine (CQ) BEL7402 Cell Viability(%) Sor: －－＋＋－－＋＋ Tet : －＋－＋－＋－＋ Inhibitor: －－－－＋＋＋＋ S 6 A B

TET: －－＋＋ PD: －＋－＋ TET : －－＋＋ PD : －＋－＋ TET : －－＋＋ SB : －＋－＋ TET : －－＋＋ SB : －＋－＋ S 7 A B Cell viability for combination of tetrandrine and PD98059 (A) or SB (B)

A HCT116 WT Bax -/- Bax GAPDH S 8 B C WT Bax - /- WT+S+T Intracellular ROS Bax - /- +S+T WTBax -/- Sorafenib : －－＋＋ Tetrandrine : －－＋＋ ** HCT116 cells with Bax-/- were not sensitive to the combination treatment with sorafenib and tetrandrine as the HCT116 wild type cells