Metronomic combination chemotherapy using everolimus and etoposide for the treatment of non‐Hodgkin lymphoma

Abstract

Patients with Non‐Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP‐16) alone and that of MCC using both VP‐16 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI‐LY‐10 and SU‐DHL‐6, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low‐dose VP‐16 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP‐16 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy‐related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP‐16 48 hours + RAD001 24 hours is the optimal method for treating NHL.

Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

“…In all patients, toxicity level is of concern and the use of intermittent MC schedules might decrease toxicity while maintaining effectivity 50 . Some clinical results 53 – 55 have also reported a successful combination of MC and other treatment approaches.…”

S100A8 promotes chemoresistance via augmenting autophagy in B‑cell lymphoma cells

“…Chemotherapy drugs can significantly increase the autophagic activity of BCL cells (43). Multiple studies have demonstrated that inhibition of autophagy enhances chemotherapy-induced BCL cell death (44)(45)(46). However, the specific molecular regulatory effects of S100A8 on autophagy and chemoresistance in BCL cells remain unclear.…”

Metronomic chemotherapy in cancer treatment: new wine in an old bottle

“…Similarly, another study revealed that metronomic temozolomide caused the accumulation of cytotoxicity through apoptosis, cellular senescence, and DNA damage to inhibit glioblastoma cells 70 . In addition to its effect on apoptosis, MCT also exerts its antitumour effects through autophagy 71 . The metronomic use of the podophyllotoxin derivative etoposide induced autophagy in non-Hodgkin's lymphoma through increased expression of Atg5, Beclin1, and LC3 71 .…”