Re-evaluation of the role of autophagy in thyroid cancer treatment

Abstract

Numerous studies have examined the role of autophagy in thyroid cancer treatment; however there are discrepancies among the reported data, with some showing the pro-survival and others the anti-survival effects of autophagy. These discrepant results appear to be at least in part due to insufficient analyses or data misinterpretation as well as improper assessments of autophagic activity. Therefore, the present study re-evaluated the regulation of autophagic activity by various anticancer modalities and examined the role of autophagy in thyroid cancer treatment in three thyroid cancer cell lines (TPC1, ACT1 and KTC1). The immunofluorescence and DalGreen findings demonstrated that cisplatin, irradiation and sorafenib were all autophagy inducers as previously reported, but, unlike previous studies using thyroid cancer cells, doxorubicin acted as an inhibitor. KTC1 cells are unique because they only responded to cisplatin. The efficacy of anticancer therapeutics was significantly higher in chloroquine or 3-methyladenine-treated autophagy-defective cells than in autophagy-competent cells, thereby indicating the pro-survival effect of autophagy induced by anticancer therapeutics, which is partly due to inhibition of apoptosis. Thus, the present findings relating to several anticancer therapeutics and three thyroid cancer cell lines demonstrate the pro-survival effect of autophagy in thyroid cancer treatment. Although the present study only involved cell lines, it provides evidence for the beneficial combination of the anticancer therapeutic modalities with autophagy inhibitors, and proposes that autophagy inhibitors may serve as a possible adjunctive therapy for thyroid cancer.

Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment

“…A similar inhibition of autophagy and stimulation of apoptosis was shown in brain [30,37], ovarian [38], breast [39,40], thyroid [41], and ATT [34] cancer cells. [41] Comments: ↑-increased expression, ↓-downregulation.…”

“…In human bladder cancer cell lines (RT4, 5637, and T24), CQ or HCQ inhibited proliferation and clonogenic formation via DNA fragmentation, increased apoptosis, the stimulation of caspases 3/7, PARP cleavage, the suppression of lysosome fusion, the accumulation of p62 and LC3-II [36]. A similar inhibition of autophagy and stimulation of apoptosis was shown in brain [30,37], ovarian [38], breast [39,40], thyroid [41], and ATT [34] cancer cells. [41] Comments: ↑-increased expression, ↓-downregulation.…”

“…Moreover, CQ therapy enhanced the anti-angiogenic effect of DOX in HUVECs [54]. However, in thyroid cancer cell lines (TPC1, ACT1, and KTC1), CQ failed to enhance the efficacy of DOX [41].…”

“…Cisplatin. CQ enhanced the sensitivity to CIS treatment in endometrial adenocarcinoma cells [35], thyroid cancer cell lines (TPC1, ACT1, and KTC1) [41], and SH-SY5Y cells [63]. In all of these cells, CQ effects were associated with the suppression of autophagy accompanied by increased LC3 and p62 expression.…”

The new insights into autophagy in thyroid cancer progression

“…evaluated the role of autophagy inducers, namely, cisplatin, rapamycin, irradiation and sorafenib in three cell lines TPC1 (PTC), ACT1 (ATC) and KTC1 (poorly-differentiated TC). Unexpectedly, compared with the CQ-cotreated group, they all play a pro-survival role in TC cells, indicated by lower apoptotic rates [ 112 ]. The reasons causing the discrepancy could be various, such as different cell models, insufficient analyses or assessments, data misinterpretation and improper group settings.…”