OBJECTIVE: Autophagy plays a vital role in homeostasis by combining organelles and cellular proteins with lysosome under starvation conditions. In addition, autophagy provides tumor cells with a source of energy. Continued autophagy will induce cells death. Here we aim to see if autophagic induction has an effect on conventional chemotherapeutic agents. METHODS: Rapamycin, or mammalian target of rapamycin and paclitaxel, apoptosis-inducing agents were used autophagy in HeLa cervical cancer cells. RESULTS: Growth inhibition of cells was not observed after the application of 0, 10, 20 nM of paclitaxel with or without rapamycin. Using a 5 nM concentration of paclitaxel, rapamycin administration inhibited cell growth significantly compared to no treatment. This implies the synergic antitumor effect of paclitaxel and rapamycin. Paclitaxel itself did not show any autophagic effect on cells but did show cell apoptosis by flow cytometry. Light chain 3, a microtubule-associated protein, which reflect autophagy, was increased with 5 nM of paclitaxel after pretreatment with 10 nM of rapamycin. CONCLUSION: These findings suggest that the autophagic inducer, rapamycin, can potentiate autophagic cell death when added as an apoptosis-inducing chemotherapeutic agent. In conclusion, the control of autophagy may be a future target for chemotherapy.
Apoptosis ; Autophagy ; Cell Death ; Flow Cytometry ; Homeostasis ; Light ; Lysosomes ; Organelles ; Paclitaxel ; Proteins ; Sirolimus ; Starvation ; TOR Serine-Threonine Kinases ; Uterine Cervical Neoplasms

Objective: To investigate the distribution of human papillomavirus (HPV) genotypes in low-grade squamous intraepithelial lesion (LSIL) cytology and the immediate risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions. Methods: This prospective cross-sectional study enrolled women aged ≥21 years that were diagnosed with LSIL cytology at Siriraj Hospital (Bangkok, Thailand) during 2017-2019. Anyplex II HPV testing was performed to detect 14 high-risk HPV cases prior to colposcopy-directed biopsy. Results: In total, 318 patients were included in the final analysis. Of those, 24 (7.5%), 241 (75.8%), 53 (16.7%) were aged 21- 25 years, 25-50 years, and ≥50 years, respectively. Eighty-two patients (25.8%) had abnormal screening results within the previous 5 years. High-risk HPV infection was found in 188 patients (59.1%) with 127 (39.9%) having single and 61 (19.2%) having multiple infections. The five most common HPV genotypes were HPV 66 (18.6%), HPV51 (9.7%), HPV58 (9.4%), HPV16 (9.1%), and HPV56 (8.2%). The immediate risk of CIN2+ was 6% in LSIL, regardless of the HPV status, 8% in high-risk HPV-positive LSIL, and 3.1% in high-risk HPV-negative LSIL. When using 6% as the threshold risk for colposcopy, performing reflex HPV testing in LSIL cytology can decrease the number of colposcopies by 40.9%, with an area under the receiver operating characteristic curve of 0.6 (95% confidence interval, 0.5-0.7). Conclusion The study findings support the idea that geographic variations affect the HPV genotype. Reflex HPV testing may decrease the number of colposcopies in cytology-based screening regions with a high prevalence of low-carcinogenic HPV.