Abstract:
Highly active anti-retroviral treatment (HAART) is currently the most effective treatment for
HIV/AIDS. Additionally, HIV positive patients receiving HAART have a better health-related
quality of life (HRQoL). Cancers previously associated with HIV/AIDS also known as the
AIDS defining cancers (ADCs), such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma
have been on the decline since the introduction of HAART. However, non-AIDS defining
cancers (NADCs), in particular, lung cancers have been documented to be on the
rise. The association between the use of HAART components and lung carcinogenesis
is poorly understood. This study aimed at elucidating the effects of two HAART
components [efavirenz (EFV), and lopinavir/ritonavir (LPV/r)] on lung cancer. This was
achieved through the use of in vitro cell biological approaches to assess cell health,
including cell viability, Real Time Cell Analysis (RTCA) growth monitoring, evaluation of
the cell cycle, and progression to apoptosis, following on drug treatments. At plasma
level concentrations, both EFV and LPV/r induced S-phase arrest, while at lower
concentrations both drugs promoted the progression of cells into G2/M phase following
cell cycle FACS analysis. At higher concentrations although cell viability assays reflected
anti-proliferative effects of the drugs, this was not statistically significant. RTCA showed
a significant decline in cell viability in response to the highest dose of LPV/r. Dual staining
by Annexin V-FITC and PI confirmed significant pro-apoptotic effects were promoted
by LPV/r. Both EFV and LPV/r exert double-edged oncogenic effects on MRC-5 and
A549 lung cells, acting to either promote cell proliferation or to enhance apoptosis. This
is affected by EFV and LPV/r altering cell cycle progression, with a significant S-phase
arrest, this being an indication of cellular stress, cytotoxicity, and DNA damage within
the cell.
