Lycorine upregulates the expression of RMB10, promotes apoptosis and inhibits the proliferation and migration of cervical cancer cells.

Although there are numerous treatment strategies, including surgery and chemotherapy, the prognosis of cervical cancer remains far from satisfactory. There is an urgent need to develop more effective, more tolerable and safer therapeutics for the treatment of cervical cancer. Lycorine is a natural plantextract that has been previously found to confer anti­tumor activities. Therefore, in the present study, the effects of lycorine and its possible mechanism of action in cervical cancer were investigated. Cell Counting Kit­8, wound healing and Transwell assays were used to verify the proliferation and migration of HeLa cells following lycorine intervention. The results demonstrated that lycorine significantly inhibited the proliferation and migration of HeLa cells. RNA binding motif 10 (RBM10) is a protein associated with apoptosis. It has been suggested that lycorine can affect the expression of RBM10. Flow cytometry demonstrated that lycorine may inhibit the initiation and progression of cervical cancer by promoting apoptosis, which may be mediated through the upregulation of RBM10 expression and increasing TNF­α levels. Xenograft mouse experiments indicated that when lycorine was injected through the tail vein, HeLa tumor growth was inhibited. Mechanistically, western blotting demonstrated that lycorine significantly inhibited the activation of the Akt signaling pathway and potentially reversed epithelial­mesenchymal transition, which was also mediated by RBM10. Furthermore, following RBM10 knockdown with small interfering­RNA, the inhibitory effects of lycorine on cervical cancer was significantly abrogated. Overall, results of the present study suggest that lycorine can upregulate the expression of RBM10 and inhibit the proliferation and migration of cervical cancer cells.

Lower lip recurrent keratoacanthoma: A case report.

BACKGROUND: This paper introduces a case of recurrent keratoacanthoma (KA). KA is a self-healing disease. Recurrence after surgical resection is rare. In this case, the local application of retinoic acid ointment after the second operation achieved a good prognosis after 2 years of follow-up. CASE SUMMARY: A 76-year-old male patient was admitted to the hospital for "lower lip rupture and scab for 3 mo". Treatment: A rectangular incision was made in the healthy tissue about 3 mm outside the periphery of the lower lip mass, and a modified Bernard sliding flap was designed to completely remove the mass. Pathology showed (lower lip) KA. When the patient returned 6 mo after surgery, the middle mucosa of the lower lip had a bulge with a diameter of about 0.5 cm. The boundary was still clear, the surface was ulcerated. A recurrence of lower lip KA was suspected and a fan-shaped incision was performed in the healthy tissue about 5 mm outside the lesion to completely resect. Pathological showed lower lip KA had recurred. Topical application of tretinoin cream was applied once a day for 3 mo. The lower lip wounds were clean at the 2-year postoperative follow-up and the mucosa was normal. CONCLUSION: Adjuvant retinoic acid treatment after KA surgical resection can achieve good results.

Effect of troglitazone on radiation sensitivity in cervix cancer cells.

PURPOSE: Troglitazone (TRO) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu(2+)/Zn(2+)-superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro. MATERIALS AND METHODS: Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 µM of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay. RESULTS: By 5 µM TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0-G1 phase cells were increased in HeLa and Me180 by 5 µM TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 µM TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 µM TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO. CONCLUSION: TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalase-mediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPARγ expression level.

Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells.

PURPOSE: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) α and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). MATERIALS AND METHODS: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. RESULTS: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 µM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARα and PPARγ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARα were not increased with FF. However, the mRNA of PPARγ was increased with FF. CONCLUSION: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARα.