Fig 1.
The computational model and chemical structure of LLL12B.
A. The computational model of LLL12B. B. The chemical structure of LLL12B.
Fig 2.
LLL12B inhibits p-STAT3 and its downstream targets in human ovarian cancer cells.
A. The effects of LLL12B on STAT3 phosphorylation (Tyr705) and its downstream targets in ovarian cancer cell lines. A2780, CAOV3, SKOV3, OVCAR5 cells were treated with DMSO or different concentrations of LLL12B. The levels of p-STAT3 and the downstream target gene proteins were determined by Western blots. B. Compared with cisplatin or paclitaxel alone, the combination of LLL12 with cisplatin or/and paclitaxel appeared to have a greater inhibitory effect on p-STAT3 and some downstream target gene proteins in CAOV3, SKOV3 and OVCAR5 cells. C. Treated with LLL12B by 0h,2h and 4h, p-STAT3 was inhibited in four cell lines, p-Jak1 was only inhibited in A2780; p-Jak2 was not detected. Total Jak1, Jak2 in SKOV3 was reduced. The total STAT3 and total Jak1, Jak2 in other three cell lines were not reduced.
Fig 3.
The effects of LLL12B, cisplatin, paclitaxel, and drug combination on cell viability.
MTT assays were performed to evaluate cell viability. A-D LLL12B inhibited cell viability of ovarian cancer cells, which were synergistically inhibited when LLL12B was combined with cisplatin or paclitaxel. The differences were found to be significantly different at *p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001.
Table 1.
The calculation of the combination index (CI).
Fig 4.
The effects of LLL12B, cisplatin, paclitaxel, and drug combination on cell migration.
Wound-healing assays were performed to evaluate the migration ability of SKOV3 and A2780 ovarian cancer cells. SKOV3 and A2780 cells were seeded in 6-well plates and treated with DMSO or different concentration of drugs: LLL12B or cisplatin or paclitaxel or the combination. The differences were found to be significantly different at ***p<0.001 and ****p<0.0001.
Fig 5.
The effects of LLL12B, cisplatin, and drug combination on cancer cell growth.
Cell growth assays were performed to evaluate cell proliferation ability of ovarian cancer cells. Cells were treated with LLL12B, cisplatin and their combination. The differences were found to be significantly different at **p<0.01 and ****p<0.0001. LLL12B alone or combined with cisplatin inhibited cell growth of ovarian cancer cells.
Fig 6.
The effects of LLL12B, paclitaxel, and drug combination on cancer cell growth.
Cell growth assays were performed to evaluate cell proliferation ability of ovarian cancer cells. Cells were treated with LLL12B, paclitaxel and their combination. The differences were found to be significantly different at **p<0.01 and ****p<0.0001. LLL12B alone or combined with paclitaxel inhibited cell growth of ovarian cancer cells.