Fig 2: SPARC, a TGF-β-induced secreted protein, is highly expressed in IPF.A, quantitative secretome analysis identifies an increased level of SPARC in the CM from TGF-β-treated MRC5 cells. Data are mean ± SD; n = 3. ∗p < 0.05. B, SPARC expression in human lung fibroblasts treated with or without TGF-β (GSE139963). ∗∗∗p < 0.001. C, SPARC expression in lung tissues from healthy controls and IPF patients (GSE92592). ∗∗p < 0.01. D, SPARC expression in lung tissues from healthy controls and IPF samples with macroscopically normal-appearing (IPF-normal) or scarred (IPF-scarred) (GSE99621). ∗p < 0.05. E, protein expression of SPARC in CM from NHLFs or IPFFs. Ponceau S staining showing total protein levels. Graph showing SPARC protein levels in CM from NHLFs or IPFFs. Data are mean ± SD; n = 3. ∗∗∗p < 0.001. CM, conditioned media; IPF, idiopathic pulmonary fibrosis; IPFFs, IPF fibroblasts; NHLFs, normal human lung fibroblast; SPARC, secreted protein acidic and rich in cysteine; TGF-β, transforming growth factor-β.

Fig 3: THC enhances the inhibitory effect of ab-PTX on BC tumor of nude mice. (a) The inhibitory effect on BC tumor in different groups; **P < 0.01, compared with THC; ##P < 0.01, compared with ab-PTX; (b) THC significantly increased the mRNA level of SPARC in MCF-7 xenograft tumor tissues; **P < 0.01, compared with vehicle control; ##P < 0.01, compared with ab-PTX; ttP < 0.01, compared with THC; (c) THC increased the protein level of SPARC in MCF-7 xenograft tumor tissues; **P < 0.01, compared with vehicle control; ##P < 0.01, compared with ab-PTX; tP < 0.05, compared with THC.

Fig 4: THC enhances the effect of ab-PTX on BC is dependent on SPARC expression. (a) Effect of si-RNAs on SPARC in MCF-7 and MDA-MB-453 cells. #1 si-RNA and #3 si-RNA have relatively high adenoviral efficacy and were selected for further sensitization analysis; (b) column plot of SPARC protein expressions; ∗∗P < 0.01, compared with scramble; (c, d) CCK-8 assay demonstrated that knocking down SPARC decreases the synergistic effect of THC in (c) MCF-7 and (d) MDA-MB-453 cells; ∗P < 0.05 and ∗∗P < 0.01, compared with ab-PTX; #P < 0.05 and ##P < 0.01, compared with THC; (e, f) upregulation of SPARC increased inhibitory effect of ab-PTX on (e) MCF-7 and (f) MDA-MB-453 cells but did not improve inhibitory effect of THC and THC+ab-PTX.

Fig 5: THC chemosensitizes BC cells to ab-PTX and increases the expression of SPARC. (a) Inhibitory effect of ab-PTX on BC cell liens at different concentrations; (c) THC enhances the inhibitory effect of ab-PTX on BC cell lines with synergistic effect. The calculated combine-treatment index q was 1.161, 1.314, 1.355, and 1.159 in MDA-MB-231, MCF-7, MDA-MB-453, and SK-Br-3 cells. **P < 0.01, compared with ab-PTX; ##P < 0.01, compared with THC in same cell line. (d) THC increases the mRNA expression of SPARC gene in four BC cell lines. *P < 0.05 and **P < 0.01, compared with DMSO.